I find it fascinating how much a pretty large group of people just hate semaglutides and seemingly need to believe that it's some kind of Faustian bargain. I'm not talking about the people who are cautious or suspicious, that's more than reasonable, but it's clear that it's not cautious optimism in many.
"No free lunch" is a reasonable question to ask when evaluating medication, if it would improve the evolutionary fitness of the majority of people. I think this is behind some of the skepticism. If Ozempic is so great then how come our bodies don't just produce more GLP-1? How come we aren't like chimps, with eternally shredded bodies and cheese grater abs, provided we get the protein to support them?
I would guess that getting fat in times of plenty was a feature and not a bug in the ancestral environment, and that's why we get fat today, which is obvious if you think about it. Still, it means GLP-1 agonists are smacking into quick "is it bullshit?" heuristics for a lot of people.
The second point I haven't seen discussed is that weight loss drugs prior to GLP-1 agonists include cigarettes, which (worst case) give you cancer; stimulants, which cause your heart to fail; parasitic intestinal worms, which can kill you but more importantly are just plain gross; and mitochondrial uncouplers, which set you on fire at a cellular level. That's a long history of miracle weight loss drugs which turn out to have horrible side effects. It's not reasonable to think GLP-1 is bad just because of other drugs with different mechanisms, but it certainly causes some skepticism anyway.
> The second point I haven't seen discussed is that weight loss drugs prior to GLP-1 agonists include cigarettes, which (worst case) give you cancer; [...]
Nicotine works just fine as an appetite suppressant without the carcinogenic tar you get from burning tobacco leaves. Similar for other stimulants or stimulant-like substances.
But I agree that they get a bad reputation, despite actually working pretty well, and with manageable side-effects: not worse than what I've heard about the nausea people get on GLP-1 drugs, and much better than the health effects of obesity.
> If Ozempic is so great then how come our bodies don't just produce more GLP-1?
We don't know. But one early signal is that you lose a lot of muscle mass and not just fat, which is not a good evolutionary adaptation if you are an endurance hunter.
> How come we aren't like chimps, with eternally shredded bodies and cheese grater abs, provided we get the protein to support them?
There are several reasons: Chimps have a higher density of testosterone receptors with a higher sensitivity than humans. Compared to humans, they are essentially roided out all the time.
Humans are also hairless endurance hunters so we naturally have much larger fat reserves (15-25% of body weight vs <10% for chimps) in order to retain body heat and have enough energy to hunt prey till they collapse from exhaustion.
> If Ozempic is so great then how come our bodies don't just produce more GLP-1?
To store calories so you don't starve. This is a failure mode of evolution and there is in fact "free lunch" when we use technology to reoptimise our bodies to calorie abundance
The other side of this is related to morals. People learned self-discipline by having to moderate their diet. Replacing that challenge with an injection is another example of a world in which people are not challenged to grow as people, but merely go out and buy something to make themselves feel or look better.
People who don't experience difficulties moderating their diet and could flounder their "self discipline" are now on a level field with people who did have difficulties with their diet. So they feel threatened by it.
Another example of a world in which people are not challenged to grow as people; instead of being happy that more people can get healthy they dismiss the medical advances as "moral failures" since they can no longer feel superior.
Honestly, this is essentially BS. I'd say that 95% of healthy weight people stay that weight because their metabolism and appetite works properly. People who stay in shape by paying careful attention to their diet are a tiny minority.
> If Ozempic is so great then how come our bodies don't just produce more GLP-1
This strays too far into appeal to nature teritory. Evolution made us fit to reproduce not to age.
As for "no free lunch" - we do have a lot of that in medicine historically speaking: iodine salt, clean water, vitamins (C, D), iron supplements, hormone theraphy, vaccines. The field of medicine is no stranger to free lunch.
none of the things you cited are “miracle weight loss drugs.” they are things people did to lose weight. these are the first class of drugs that actually cause people to lose weight.
Amphetamine is actually a very effective weight loss drug. And it's sort of orthogonal to the fact that it's a stimulant. Stimulants in general can cause an acute reduction in appetite and temporary weight loss. This tends to stabilise with tolerance, however. As someone with obesity and ADHD, thus was my experience with methylphenidate treatment. And I used to think the weight loss effects of amphetamine were analogous until recently.
Amphetamine and methyphenidate(MPH) have very different ways of acting as stimulants. MPH is an inhibitor of the dopamine transporter(DAT) and the norepinehrine transporter(NET). These cross-membrane proteins essentially "suck up" the dopamine or norepinehrine after neurotransmission, thus regulating the effect. MPH inhibits this process, increasing the effect. This is called a norepinephrine/dopamine reuptake inhibitor(NDRI). Cocaine also works like this, as well as the antidepressant wellbutrin(bupropion).
Amphetamine on the other hand, is a bit more complicated. It interacts with DAT/NET as well, as a substrate, actually passing through them into the neuron. Inside the neuron, it has a complex series of interactions with TAAR1, VMAT2, and ion concentrations, causing signaling cascades that lead to DAT reversal. Essentially, enzymes are activated that modify DAT in such a way that it pumps dopamine out of the neuron instead of sucking it up. How that happens is very complicated and beyond the scope of this comment, but amphetamine's activity at TAAR1 is an important contributor. As such, amphetamine is a norepinephrine-dopamine releasing agent(NDRA). Methamphetamine, MDMA, and cathinone(from khat) also work like this.
Anyway, recently I was reading about TAAR1 and learned something new, namely that TAAR1, besides being and internal receptor in monoaminergic neurons, is also expressed in the pancreas, the duodenum, the stomach, and intestines and in these tissues, TAAR1 activation will increase release of GLP-1, PYY, and insulin, as well as slow gastric emptying.
So in essence, there may be some pharmacological overlap between ozempic and amphetamine(I'm still looking for data on how significantly amphetamine reaches TAAR1 in these tissues, so unclear what the relevance is. But amohetamine is known to diffuse across cellular membranes, so it's likely there is an effect).
Also interesting, amphetamine was recently approved as a treatment for binge eating disorder. Not only because it causes weight loss, but because it improves functioning in the prefrontal cortex(crucial to its efficacy in ADHD), which is apparently implicated in the neuropsychological aspects of BED as well.
The American Tobacco Company marketed cigarettes for women's weight control in the 1920's. Lucky Strikes 'Reach for a Lucky" campaign was a big example of this as well, although they marketed it as an appetite suppressant rather than simply a miracle weight loss cure.
Keeping in theme, Ozempic specifically has already been marketed off label as an appetite suppressant, rather than a pure weight loss drug. That's a more modern construct in its brief history.
I was kind of scared of these when Ozempic starting picking of steam for weight loss. I was worried that this would be having more negative effects. Turns out, generally speaking, if used with you doctor, these things are pretty safe, especially comparatively to some of the negatives of being overweight.
And then I saw some of the stories on HN about how it's changed peoples lives for the better. And then people in my life started taking it and singing its praises. I'm very bullish on GLP-1s now and I've very excited to see all the lives it improves. I'm not saying this thing is 100% miracle with no downsides, but this seems to be a generally large net positive.
It's a bit hard for me to comprehend how big of an impact this can have for someone since I've been very fortunate to never struggle with my weight, but I'm (slightly embarrassingly) tearing up writing this because of how many people I've seen have huge positive effects on their physical and mental health (due to body image).
The skepticism people have towards metabolic dysregulation models of obesity is too much.
We know for a fact the inverse happens: girl starves herself for years to slim down to become a ballerina, eventually decides it's not worth it and tries to stop being so dangerously thin and... can't. She never feels hungry. Every time she eats she can only stomach a few bites before pushing it away. Just eat ice cream? Instant puke. She cannot gain weight no matter what.
Obviously she broke her metabolic system and she obviously did it through diet.
Yes it's possible for some skinny people to gain weight. But that doesn't mean every skinny person simply can decide to be fat just by eating. It's like climbing Mount Everest for some skinny people to put weight on, even if they really desperately want to.
I don't think the situation with obese people is all that different.
This concept would be hard to grasp for me if I did not know personally a person facing such issue. I don't think most people can understand that "just eat more" does not work in such cases, because most people can eat just fine even if not really hungry.
> because most people can eat just fine even if not really hungry.
I literally cannot imagine how this is possible. Don't you feel full? Doesn't your body start refusing to swallow? Doesn't the food turn tasteless and start making you nauseous? 100-200kcal over your BMR, sure, but beyond that?
I didn't buy into the whole metabolic health thing -- I thought a calorie was a calorie. But as a person who couldn't lose weight for years due to insulin resistance, just a single daily dose of metformin enables me to lose weight. I was advised to take either that or a miniscule dose of a GLP-1 agonist.
For the pure fat experience I suggest corticosteroids, lithium or a random antipsychotic. Insulin is also very useful here, but a tad dangerous.
If it has to be muscle mass, then anabolic steroids of course are preferable. But beta adrenergic agonists like clenbuterol also seem to have some effect.
I don't want you to consider it among the flippant replies here but definitely alcohol will work up to a point, it's somewhat of a contradiction though because severe alcoholics are usually quite malnourished and thin.
This spiked my interest, so I looked around and found a 2018 paper (DOI: 10.1039/c7fo01715d) which, when fed into an LLM, gave me the following information (edited for brevity and clarity). Please note that I did not verify any of the LLM's claims, so take with a pinch of salt. Or pepper.
The study tested a black pepper-based beverage (BPB) containing 20 mg gallic acid equivalent of polyphenols.
Key findings:
- Lowered hunger by 17%
- Reduced desire to eat by 15%
- Decreased prospective food consumption by 17%
- Increased satiety by 14%
- Increased fullness by 16%
What didn't change:
- Blood glucose and insulin responses
- Gastrointestinal discomfort
- Gut hormones (PYY and GLP-1)
Approach:
- The beverage was consumed 10 minutes before a meal
- It contained water-extracted black pepper compounds (not piperine, which isn't water-soluble)
- The extraction used hot water at 90°C for 3 minutes
If you want to try this:
1. Make a black pepper extract: Steep 20g of black pepper in 100ml of hot water (90°C) for 3 minutes, then strain and dilute with 900ml of water
2. Timing: Consume about 10-15 minutes before meals
3. Monitor your response: Track your appetite sensations to see if it works for you
Critical notes:
- The appetite-suppressing effects appear to be from water-soluble polyphenols (like apigenin and luteolin compounds), not piperine
- The study was short-term, so long-term effects are unknown
- Individual responses may vary
- This won't affect your blood sugar or metabolism directly
Gaining weight works by putting more fuel into your body than you use. That's physically the only way, there is no way to synthesize energy. Because of caloric density limits, there is no substitute for putting a certain amount of stuff in your body. A pill can physically not contain enough calories.
There are options around that, but that depends on what's driving your personal energy deficit. What's the job that the weight gain intervention needs to do for you, that whatever you try to eat right now does not? What's motivating your current diet? Are you for example disgusted by swallowing anything at all? Are you more partial to liquids than whole foods? Do you dislike sugar in particular?
It's great because we had no other way to address this problem at a population level. Not any realistic ones, anyway.
Like, I figured we were just never going to solve it, given the two possibilities were "radically re-engineer US culture such that moving to the US doesn't make previously-skinny people fatter" (with other countries heading the same direction as us needing to make similar moves, one supposes) or "find a miracle drug". Neither seemed likely. Turns out, decent odds we've managed the latter! Which was always the more likely of the two, but I still wouldn't have rated it as very likely.
I helped my dad lose 50 lbs by finally, after 10 years, getting him to give up bread, sugar, potatoes.
It took buying him 2 months of a bluetooth glucose monitor. Once he saw what certain foods do, he believed me finally.
At 65 years old, healthier than I remember since he was 40 and I was a teen.
It doesn't require some weird injection.
Individually, there's (previously) been nothing better to suggest than "try harder (and, maybe, smarter)".
Statistically it was almost useless, but it's the best we had. It's not bad advice exactly, it's just extremely unlikely to work for long-term, sustained weight loss.
It also very much appears to be the case that weight gain and loss are heavily influenced by environmental factors. Skinnier countries aren't skinnier because the people there have more willpower, it seems, but because they live in a skinnier country and are surrounded by the culture, laws, physical layouts of the created world, et c., that come with that. It'd be kinda weird if we expected "just try harder" to work very well when that's evidently not the mechanism by which skinny countries are skinny. Alternatively, if it is willpower doing it, we're just adding a step, because then it appears that environment strongly influences willpower, instead, since the same observations hold.
Sure, sometimes it works for individuals. In fact, it often works temporarily, causing a yo-yo effect. It can work for long periods (many years without a slip) but that's rare.
If your solution to the obesity crisis is "people need to try harder" your solution is demonstrably not helpful. Can it work for one person? Yes. Over a population, will it? No, it won't, it's amazingly ineffective, even very expensive high-touch interventions involving multiple experts aimed at weight loss and lifestyle change and such are wildly less effective than "inject GLP-1 agonists" or "move somewhere skinnier".
> If your solution to the obesity crisis is "people need to try harder" your solution is demonstrably not helpful. Can it work for one person? Yes. Over a population, will it? No
Are you an individual or a population though? Take off the telescopes (and data, and science), and look at the world through your own eyes.
No one needs (or can) to address the obesity crisis in the population. The only crises that can be solved are the ones individuals find in themselves.
having the understanding of the science and self motivated enough to make lifestyle changes already puts you a couple standard deviations out of the population average, such that I don't really think its helpful as a comparison or something to model after
Run a study of your approach and show good results over a cohort for 2+ years and you'll make an entire sub-field of medical scientists very happy.
[EDIT] It's not that your approach can't work, it's that if (for example) people had as hard a time following the directions for condoms as they do following diet & workout plans, we'd never allow condoms to be sold as contraceptives, they'd not even be close to being OK to promote as useful for that purpose. It wouldn't matter if a few people could follow the directions and it worked 100% of the time for them.
I assure you, not buying bread and pastries for your family is a lot easier than correctly using a condom in the heat of the moment. Which is why most people don't use them and use pull out instead. Because even that is easier and better if done right. (I know when to pullout, I don't know if a condom broke before it's too late).
Anyway, it does work, people just aren't told to do it firmly. Doctors dance around it.
The zeitgeist has pushed the idea carbs/grains and sugar are terrible over the last 40 years on and off, so that seems to say more about the medical industrial complex, than anything. That's fair, but if that message has been pushed so consistently, why didn't we see a real decrease in the consumption of those things and the associated weight loss?
I find that almost all doctors give useless advice. On multiple occasions I've been advised that there was nothing wrong but they can run a scan "if I insist" and then bam, the exact problem I expected shows up clear as day.
Doctors don’t get paid for writing prescriptions. They don’t get kickbacks for writing prescriptions. A small subset of doctors are paid by pharmaceutical companies to run trials or provide expertise, but you can look that up since it’s publicly available information, and it’s not based on them prescribing you anything.
At most a drug rep comes by and brings donuts or something to talk about their new drugs.
Increased reporting requirements and a cap on the value of these gifts that is far too low for box seats.
My wife's a physician, and I've seen these things change dramatically. Sometimes some food for the whole office will get dropped off. Or donuts. No one's getting box seats to a pro sports game anymore.
They get paid in lower risk deductibles. If a patient demands a drug they saw on commercials, the doctor can reduce liability by prescribing it in many cases.
Huh? Drug reps have scorecards for the doctors they call on and throw perks at the top performers or influencers. It also depends on the speciality - dermatologists working for price equity mills are almost evaluated like salespeople. Source: girlfriend is a rep.
He could have lost all that weight and still had bread, sugar, and potatoes but instead he gave up what he clearly enjoyed. Now he gets to live out the rest of his life fighting cravings, telling himself he's not allowed to enjoy food. How utterly sad.
Believe me, cutting out bread and sugar completely is 10x easier than some kind of lifelong moderation for a person that has struggled for it already for most of his life.
And he is extremely happy with his new sugar and bread free life of increased mobility, less pain, and much lower blood pressure. At 64, he's learning how to ride a dirtbike and doing pretty well at it.
The choice is no longer between "cutting out bread and sugar completely" and "some kind of lifelong moderation for a person that has struggled." The choice is now between "cutting out bread and sugar completely" and "removing the struggle to moderate bread and sugar."
You're clearly an advocate for your father making healthy choices. So why would you advocate against the use of a drug that makes that easier?
Telling your mind to do a thing is only ever easy in retrospect and when you find a "trick" that works for you. For some people that trick is getting clear feedback about glucose levels in your bloodstream. But any trick that works for one person might not work for the next. So it is good that there are many approaches.
Obviously it’s not much easier or the drug wouldn’t be so valuable.
People make such a moral crusade of this - the drug works, people will take it. Behavior modification works in theory and fails for most in practice. Even for those that can make it work usually don’t hold out indefinitely.
I made no moral statement. Behavior modification has worked great for several formerly obese people that I know. They made permanent lifestyle changes without relying on drugs. I really don't care whether people take weight loss drugs or not but the reality is that there are cheaper and safer alternatives.
If changing your habits was much easier then we wouldn't need these medications and the world wouldn't keep getting fatter. People have known how to not be fat for a long time, yet the obesity rate has been rising worldwide, even in countries that have traditionally been skinny.
It's not like fat people on the whole are ignorant of how to become not-fat and never attempt to do so.
Because people are choosing deliberately to get pleasure to eat unhealthy stuff instead of being healthy. And that’s a reasonable thing to do. Immediate pleasure trumps future hypothetical gains.
And it’s exactly the same situation with financial education, debt, university degrees, or in general any long term endeavors that requires the sacrifice of the immediate pleasure.
Of course, we still have a non trivial percentage of people that suffer from eating disorders, and use food as a way to emotionally regulate themselves because that’s what they learned as children (child is unhappy, give him a candy…).
> Now he gets to live out the rest of his life fighting cravings, telling himself he's not allowed to enjoy food. How utterly sad.
I don't understand what drives people to write such intentionally asinine comments. Do you get off on hurting others or something?
There were quite a few foods I let go of when I decided to drop weight. Can't say I miss them much, certainly not to the extent to say something like "wow, i can't enjoy food anymore" or "now i'm fighting cravings all the time!!". And I legitimately have no interest in reintegrating them into my diet.
Turns out, some kinds of food are just dumb to consume, and my enjoyment of them is legitimately secondary. To the extent that discovering how harmful they were, they became inherently less enjoyable, and it was well possible for the habits and the cravings to subside over time. You don't try to go hit a balance with crack addiction, why would you try to hit a balance consuming 5 bazillion calorie rubbish?
Cutting out certain classes of foods from one's diet is absolutely possible and there's nothing necessarily wrong with it.
Bread, sugar and potatoes exist on a spectrum from highly processed/refined (truly problematic) to minimally processed whole food versions (nutritionally valuable). There's no reason to give up minimally processed whole food versions of these.
What a bizarre, illogical comment. Did you even read what @throwawaylaptop wrote above? While most of us can handle she carbs just fine, some people have to pretty much eliminate them (regardless of processing level) in order to lose fat.
I helped my dad lose 50 lbs by finally, after 10 years, getting him to give up bread, sugar, potatoes. It took buying him 2 months of Ozempic. Once he saw what stopping the cravings for certain foods can do, he believed me finally. At 65 years old, healthier than I remember since he was 40 and I was a teen. It doesn't require some weird bionic arm implant.
Yes, if you don't need it because there is a natural method that starts fixing your problem in the first week (like cutting all carbs does for being fat), then injecting insulin for your easily fixable problem would also be up there with injecting weird stuff into yourself.
If you told millions of people that bread, sugar, pasta and bread are basically killing them, and to flat out stop eating them.. you probably would help people lose weight (and save many lives too).
My dad has finally understood that grains are for people that need help maintain weight or gaining weight.
But millions of people are being told; "cutting carbs helps with losing weight" is, I dare to argue, commonly known.
> No fat person should ever be eating them.
This is absolutism and controlling. Carbs have their place in a balanced diet, but key emphasis on diet. Too much (like the US diet) isn't good, none at all isn't good either. Everything in moderation. I don't understand why dieting / weight loss conversations are always going into extremes and absolutes.
You don’t think people ate carbs 3 times a day in the past? The majority of humans for the majority of recorded history have eaten some kind of bread, rice, potatoes, porridge, or corn with the majority of their meals.
Also in the majority of recorded history being fat was a sign of wealth. I don't think the majority of humans had a surplus of carbs available to overeat them. It's not that carby foods are inherently bad, there's just something bad about the way they fit into modern society, for some people.
Modern wheat is a very modern invention. You have to be pretty gullible to believe that something that has only existed for 50 years has existed for millennia.
I think its great you helped your dad lose weight but what is your issue with others choosing a different path? The health benefits of losing weight are massive . Why is it important to you that they do it how you want them to do it? Study after study has sung the praises of GLP-1s.
It appears that your major issue is that you are simply angry people are taking a short cut. Which seems odd, why would it bother you how someone lost weight, why not just be happy for them?
I got on GLP1s in January. I went from 6'1 240lb to 209lbs with defined abs benching 405lbs at 46 years old.
I've worked out my entire life but never been lean like this. I like eating bread (steak, eggs, toast, ketchup and hot sauce is perhaps the single greatest breakfast in the history of the world. The toast is very important!) and potatoes are freaking incredible (mashed with Worcestershire sauce... bruv).
The bulk of my calories are protein but I generally eat what I want if I desire it. I just desire less of it. I had a roast beef sub from Jersey Mike's today with my kid, it was delicious. Their honey mustard is the bee's knees. I had a medium sub though and not a large.
The only change is now I essentially don't eat after 6pm. I just set that goal and the GLP-1 helped me keep it. The only side effects I have had is lower cholesterol and lower BP and that is while running 700mg of test. I'm going to hop on metformin next month after this cycle and target eliminating the fatty liver markers I have had for the last 20 years.
They work friend, they are good for you and they make people live happier healthier lives.
Heroine would also help them lose weight also. Maybe cocaine too, but I'm not sure. So it's not "all that matters".
What matters is, are the negative side effects and long term consequences better for you than the alternatives. One of them is "remaining fat". The other is "doing what other people have proven works.. cut all carbs".
You are showing your own ass with this ridiculous analogy. What are the negative effects of ozempic? Because the negative effects of heroin (not "heroine") and cocaine are well known and grossly outweigh "not being fat."
From people I know that have used Ozempic/Wegovy, the side effects are basically that they get a bit nauseated a few hours after an injection. That's it.
> Like, I figured we were just never going to solve it, given the two possibilities were "radically re-engineer US culture such that moving to the US doesn't make previously-skinny people fatter" (with other countries heading the same direction as us needing to make similar moves, one supposes)
Moving to higher elevations in the US causes people to become less fat, so you can do this by moving to Colorado.
And not just weight loss, but the people I know on GLP-1's have also significantly cut back on alcohol. I think there are ongoing trials around GLP-1's and general addiction.
I've heard similar for gambling, and as one of the sister comments said, things like video games. I'm so curious to understand _why_ that effect is there, but I've heard this so many times now that I do believe that it exists in some capacity. Such an interesting world we're opening up here.
My hypothesis is addiction is generally a secondary application of overeating. Getting pleasure from eating a surplus when you’re not hungry is adaptive (or at least was for most of human history).
In a lot of ways these other behaviors are similar, it wouldn’t shock me if it’s a shared underlying mechanism originally to encourage eating a calorie surplus.
Every person I know who tried to give up smoking has the same story - they were successful for a while and then they encountered some stressful moment (exam, work deadline, etc) and they fell off the wagon. One explanation could simply be that normally we have food stresses which manifests in general stress which we relieve via video games or whatever else. If these drugs turn down the volume of hunger then maybe this has the benefit of reducing the need for stress relieving behaviours in general.
I’ve taken a GLP for two years. It resets your dopamine reward system. It helped me lose 80 lbs and I’m running now. Zero craving for alcohol and sugar. But, my libido is like 3x lol.
If some rando internet dude thinks I’m weak or stupid, fine with me. It’s a drug that has improved my life in ways that are difficult to describe.
I wouldn't speculate on the cause of action, however all those activities are linked by activation of the dopaminergic reward circuit, so semaglutides might have some broad based anti-addiction properties by moderating dopamine activity.
It helped me cut back on my drinking significantly. I'm not an every day drinker but a weekend binge drinker and the amount I drink when I drink is down by I'd estimate by around half or more.
I have an Adderall prescription, although I rarely use it. Adderall lets me focus on things longer, with distractions staying in the background. If anything, Adderall makes me too focused on a task.
If I were doom scrolling when Adderall kicked in, the risk is I'd continue doing it for hours.
However, amphetamines such as Adderall were also sometimes prescribed for weight loss. I'm surprised it was done so rarely before Ozempic was a thing. They were quite effective.
The side effects of adderall are pretty bad. If I'm on a dose that's high enough to suppress my appetite, then I get a very bad crash in the evening. I start to feel like if I want to enjoy life after work, I need to take another adderall to feel normal. That disrupts sleep, and then things start to get really bad.
That may be a correlation without causation. Don't know if you lost much weight, but if you did, a huge benefit of losing weight is to increase the level of tonus, and suddenly activities that require no tonus (playing video games, watching TV) become less compelling relatively to other activities.
Not for me, in fact my diet involed not taking any dessert, which GLP1 made fairly easy, so I ended up allowing myself to drink a couple of glasses of wine in the evening, which I never did before. I never noticed an alteration of the sense of taste, just a general feeling of satiety (particularly on an empty stomach).
Though many people mention feeling sick as a common side effects, I can very well imagine that they would lose any pleasure from food and drink.
Friend of mine took it for his wedding and completely stopped gambling after having a problem with it. He says he's never been more focused in his life on being productive with work and family.
The cynic in my thinks this will its undoing. Some huge fraction of alcohol profits come from a small portion of drinkers. If these G* peptides help these poor people their drinking under control, it would take a huge wrecking ball to the profits, and thus to the taxes. Can't have that.
They're very expensive drugs so it would be one lobby against another. However given that they're so expensive, I would think that broke, uneducated alcoholics just won't have access to them, so those profits are safe...
Reduced healthcare, policing, and other costs that are paid for with tax dollars from lower alcohol consumption would almost certainly be a net gain over the piddly tax revenue from alcohol consumption sales.
There's still plenty to learn about long-term effects, but it's hard to ignore the sheer volume of real-world stories from people saying it gave them their lives back
We think obesity is basically going to be gone in <7 years. GLP1s don't work for everyone, and the side effects can be severe, but this these drugs are basically safe, and incredibly effective.
This is going to accelerate when every one and their mother (with industrial capacity) starts making generic Ozempic/Wegovy (Semaglutide) next year due to Canada's patent protection lapse[0].
Theoretically, the tidal wave of generic Semaglutide wouldn't hit the US or EU due to patent protections there... But see the aforementioned note about capitalism.
Note that there is already generic Liraglutide as well:
But having any of these available is a step change.
> (...who might be the target market - being overweight might be a disease of affluence)
This might be true on the margin but is mostly untrue these days. The lack of access to healthy unprocessed food and the free time to exercise are becoming increasingly problems for those who are NOT wealthy.
This is the killer feature of Semaglutide and GLP1 Receptor Agonists widely. They were originally commonly thought about as digestion-slowing, and while that is part of it, the real change is that it's a brain drug.
Uh, so, first, I'll say that bariatric surgery is largely a successful (if extremely invasive) intervention. It is not the case that people who do that surgery somehow compensate eat back to the same level -- on average, they don't. And second, the GLP-1s just massively reduce the urge to snack/eat. I'm sure they are less effective for some people than others, but on the whole they are miraculously effective for the population that overate habitually (the obese).
Many people (will only speak to America), view being fat as a literal moral failing. Gluttony or overeating are not the sin, but being fat.
(From that perspective:)a miracle cure that allows someone to stop being fat is like an indulgence (in the Roman Catholic sense). It’s a cheat, a shortcut that allows the unworthy to reach a state they do not deserve.
My opinion is to wait long enough to validate there are no long term harms, but beyond that, yeah, adjust the priors, it could be a modern aspirin.
> Many people (will only speak to America), view being fat as a literal moral failing. Gluttony or overeating are not the sin, but being fat.
I feel like I've seen and heard more of the opposite: The trend is to avoiding anything that might make someone feel blame for arriving in their situation.
With obesity the trend is to blame some combination of "our food supply", trending science topics like microplastics or the microbiome, and genetics.
I've heard countless people explain to me that dieting doesn't work for them. It's not hard to find people claiming they ate <1000 calories per day and still gained weight. Even Eliezer Yudkowsky, a figurehead of the "rationalist" movement, has written about "metabolic disprivilege" and claimed that his genetics do not allow him to lose weight through dieting. This thinking runs deep.
What's interesting about GLP-1 inhibitors is that they modulate the intake portion of the diet, which shatters these previous notions that some people had "metabolic disprivilege" and simply could not lose weight by reducing caloric intake. They just make it easier to reduce food intake.
> I feel like I've seen and heard more of the opposite: The trend is to avoiding anything that might make someone feel blame for arriving in their situation.
> I've heard countless people explain to me that dieting doesn't work for them.
I think you're being a tad reductive – "dieting right now doesn't work for me for reasons I can't control" and "reducing calorie intake will help me reduce weight" aren't necessary contradictory, and don't imply "I'm going to attribute it all to biology/blame it on something general".
Anyway, let me assert the opposite: as a partner of a nutritionist who's talked (with anonymity) about her clients, the majority of the people she's worked with, who struggle with sustainably reducing calorie intake over the course of years, come to dieting with that logic, and _then_ struggle against specific barriers, and _then_ blame themselves. (A recent example: "because of my work schedule I don't get enough sleep, which leads to weight gain and time only for frozen food – on top of my predispositions".)
In that case, GLP-1 inhibitors as an intervention _complements_ the way her clients think about dieting.
I was responding to a comment about Americans blaming others, not dieters blaming themselves.
The concept of "blame" isn't really helpful anyway. The problem I frequently see is that blame becomes something to be avoided, which turns into a game of externalizing the source of the problem, which makes people think the problem is out of their hands.
A similar pattern happens in addiction and addiction counseling, where well-meaning friends and family try to soften the blow by telling the person that the addiction was not their fault, it was the result of their circumstances or bad influences. Addiction counselors have to undo this thinking and find a way to gently get the person to take some ownership of their role in arriving at the problem, which is the first step to having some control over correcting it.
For nutrition, when people convince themselves that they have a hidden metabolic disadvantage that makes caloric restriction not work for them, they're more likely to give up than anything.
> Even Eliezer Yudkowsky, a figurehead of the "rationalist" movement, has written about "metabolic disprivilege" and claimed that his genetics do not allow him to lose weight through dieting. This thinking runs deep.
I thought EY's point was different. Am I misremembering? I thought it was about not being able to do mental work productively when dieting enough to loose weight(maybe maintain a low weight too, though I do not remember that being mentioned explicitly).
It's a long story. His description of "dieting" was extreme calorie restriction. He was eating something like 800 calories per day (don't quote me on the exact number) and then was complaining that he didn't feel well when doing that (to the surprise of absolutely nobody).
Then it turned into a false dichotomy between the 800 calorie severe calorie restriction or no dieting at all. Then he just started declaring he'd delete any comments that suggested dieting.
It's clearly both. Someone with stronger motivation to stay healthy can survive in adverse conditions, but a society that pushes unhealthy lifestyle harder is going to catch more people out. It's obvious that Americans aren't just all individually lazier than the rest of the world. Their cities and food are unhealthy.
Genetics do factor. It's not just a question of genetics affecting metabolism. People literally don't feel hunger with the same intensity as one another. It's like sex drive. There are both very horny people and asexuals out there. There are also people who routinely forget to eat. For many people though, the notion of "forgetting to eat" seems completely alien, because those signals are much stronger for them.
I agree with you, but it's important to remember that "dieting down" is way harder for a lot of people. I am and always was skinny through my life. Whenever I need to eat less, I can do it without much effort. However, I have friends who would faint if they tried to diet down the way that I do. I don't know why that happens, but I've seen happening and it changed my perspective about this subject. If Ozempic can help with that, I will never criticize someone who uses it.
And also the idea that it is "easy" to lose weight is completely out of touch. If it was there wouldn't be millions of people trying hard, spending money on trying and failing for decades, and entire businesses addressing that.
RFK Jr's "let them eat less" is paradoxically the modern version of "let them eat cake"!
> And also the idea that it is "easy" to lose weight is completely out of touch. If it was there wouldn't be millions of people trying hard, spending money on trying and failing for decades, and entire businesses addressing that.
This is a touchy topic, but I would like to point out that you're missing the obvious confirmation bias that comes with this observation.
There are many people who modulate their weight by changing what they eat, how much they eat, reducing snacking, meal planning, and changing their shopping habits.
You don't see them among the millions of people failing to lose weight or paying for expensive solutions because they quietly solve their problem.
I'm also not suggesting it's easy, but we should acknowledge that many people do successfully control and modulate their weight through dietary and habit changes. There's a survivorship bias problem that occurs when you only look at the remaining sub-group who has the most difficulty with this.
> I'm also not suggesting it's easy, but we should acknowledge that many people do successfully control and modulate their weight through dietary and habit changes.
For example: weightlifters. It’s standard operating procedure to “bulk up” - periods where lifters overeat to promote muscle growth - and then diet to “cut” weight to drop the fat gained during the bulking period while keeping the muscle. They tend to be extremely motivated individuals though.
> It's not confirmation bias when it's more then 1 in every 3 people
If you construct your argument to exclude the 2 out of 3 people who are not overweight and then point out that the remaining 1/3 is overweight, that's the definition of confirmation bias.
It's also a disingenuous argument because not all of those 40% are actively trying and failing to modulate their weight in any way. Most people just don't care.
and there are people who don't get fat no matter what they eat. Not sure what difference it makes to the millions of people I am refering to. Not even sure what is your point.
> and there are people who don't get fat no matter what they eat.
This is a myth.
When you actually track what these people eat, their daily caloric intake averages out to numbers you'd expect. At best, the difference between "fast metabolism" and "slow metabolism" people in studies comes out to a couple hundred calories per day.
You may witness someone consume 2 pizzas and a soda in one sitting without getting fat, but that person is consuming fewer calories for the rest of the day or the week to offset it.
I think what they mean is "they eat whatever they want and however much they want" and still don't get fat.
Some people just only want to eat an amount that doesn't get them fat. They aren't using any willpower or anything, they just don't want to eat more than a healthy amount for them.
I am not one of those people (I am overweight when I eat as much as I want), but I am for other things. For example, I don't drink very often (only maybe 10 times a year) and don't get very drunk when I do. I just don't feel a desire to drink very often. It takes zero self discipline to not drink for an extended period of time because I don't have the desire for it.
On the other hand, many alcoholics struggle mightily to avoid drinking. It takes all their willpower to not drink.
Everyone is different in their ability to avoid different addictions.
What you're referring to, is the basic concept of thermodynamic calorie in/calorie out.
Yes, you can "just" reduce food and lose weight if you hit deficit numbers.
But if you don't do it correctly, you'll feel like trash, you'll suffer bad cravings, and put yourself in a stressful mental situation for days, possibly putting your job at risk.
You have to:
- Eat less than what you're already eating
- But enough to nourish yourself so you keep being in good shape for your work and hobbies
- Manage hunger
- Make the change sustainable so you can keep doing it for the rest of your life.
It's specially hard when your work is entirely sedentary, you live alone and, ironically, when you have a salary that let's you order food every day.
A lot of people don't have it hard. Maybe because they have someone cooking for them at home, because they meal prep the entire week, or because their work is so physically intensive they can just wing it and burn everything with what they need to do for a living anyway.
Inaccurate in my opinion. Let's say you eat 2500 calories a day usually. But you want to lose weight so you reduce it to 1800.
Except your calories are from pop tarts.
If you ate 100 calories of pop tarts every hour you're awake for total of 1800 calories... At the end of the month you'd be fatter.
If you ate 1800 calories of pop tarts once a day in 1 hour, you might maintain weight or loose a little. Maybe.
If you had 3600 calories of pop tarts in a few hour window, and then didn't eat again for 48 hours, you'd lose weight in a month.
Insulin control is 99% of losing weight. Yes thermodynamic blah blah, but unless you pay attention to hormone control that controls metabolism in general, it's not going to work without insane willpower to keep your 'calories out' higher than your body wants.
If you repeated the 3600 calories every 48 hours with beef instead, you'd lose weight like never before.
Insulin control is about managing hunger more than a direct cause for weight.
You don't even need to do keto or wacky "just meat" diets to handle insulin. Protein consumption prevents insulin spikes for around 1-2 hours after eating.
Also, proteins and fats slow down digestion.
Turns out, the good old Mediterranean diet is spot-on for a healthy lifestyle.
It is only thermodynamically impossible if you assume 100% efficiency in energy extraction from food, but in practice we only extract a very small amount of energy from matter. Thermodynamically you could extract ~10^12 kcal from a Pop Tart if you converted its mass into energy.
Not that I agree that for a human metabolism meal timing makes much of a difference in energy extraction, but it wouldn't be thermodynamically impossible.
It's insane to me that people keep talking about the energy in part. Forget that.
Realize that WHAT you put in can change what energy out is.
If I gave you 1800 calories of vodka at 8am, would your use the same amount of energy during the day, and even make it to your 7pm gym? No.
Ok, well sugar isnt exactly the same obviously, but it can also affect what you do that day, how your body acts, your brain even.
Your energy out gets totally messed with after you have tons of alcohol for obvious reasons.
Something similar happens on sugar/spiked insulin levels. Can you willpower through it and increase your energy out by running til you drop dead and lose weight? Sure. But it's not easy.
What's way easier is not having the insulin spike in the first place.
Yes it can affect what you do. That's the calories out part of the equation.
Nobody claims that the quality of what you eat has no effect on you, but every study shows that if you maintain the same calorie intake and expenditure it doesn't really matter how you consume the calories or how you expend it.
Well then luckily that shows you hopefully how bad studies are.
Because I assume that you agree that eating 100 calories of Pop-Tarts per hour for 18 hours for 30 days, would give you a different result than eating 3 days worth of Pop-Tarts in a few hours once every 3 days for a month.
To not understand that would mean that while believing some studies, you completely ignore all the studies that have been done on insulin and weight gain.
> Because I assume that you agree that eating 100 calories of Pop-Tarts per hour for 18 hours for 30 days, would give you a different result than eating 3 days worth of Pop-Tarts in a few hours once every 3 days for a month.
I agree that you would feel very differently in those situations and it's likely you wouldn't spend the same amount of energy unless you really make an effort to do it.
I don't agree that if you do make an effort to spend the same amount of energy you would have different results with regards to weight loss.
Two weird assumptions here...1, that massive amounts of constant blood sugar/insulin don't affect metabolism.
2, that in the face of crazy long term insulin/hormone disruption, people will continue to be just as active as if they had a sane diet of mostly meat and vegetables.
Are you saying raising your insulin levels hourly, 18 times a day, will not do anything to your metabolism? Did you even read my post, or did you just instantly reply with the same pedantic reply which my post was specifically meant to address?
The first law of thermodynamics applies to closed systems, which your body is not. Yes it is true that, very broadly speaking, eating more results in weight gain past a certain point. But first principles are not the most proximate reason for that by a long shot.
That's exactly why I liked being on keto. Never felt hungry, had way more energy, mental health improved a lot. No other diet had those effects. I've been off it for a while and I feel gross again.
Right, so exactly like I said, it's very simple. If you want to lose weight, reduce calories.
If you add extra modifiers like "I want to feel great while doing it" and "I want to lose weight while sedentary" and "I want to continue eating whatever stupid thing I want" and "I need to be able to scroll tiktok for at least 3 hours, leaving no time for cooking", it gets much more complicated.
Side note: LOL at "but if you're craving food you might get fired!!1!" - this is professional victimhood at its finest.
Even then, limiting calorie intake isn't all that difficult; there's a reason why intermittent fasting took off and so many people were getting results from it.
Not necessarily. Some people respond well too intermittent fasting but not everyone. Some people respond to keto but not everyone. And just because you respond doesn't mean it's gonna take you to where you need to be.
I've always been skinny but for some reason I've gained weight recently. Even with keto, intermittent fasting, tirzeptide, and workouts twice a week I have only lost 5 lbs in months. When I was skinny and forgot to eat, I would feel a little crappy but still could function. Now I begin to feel incredibly depressed, I can't sleep nor focus. This solidified it to me that there's a circuit in your brain that controls feeding and if it's out of whack it'll punish you until you eat. Dieting takes months and no one can go that long without sleep. So it's still a practical problem, its just hard to see if your system is well calibrated.
> Even with keto, intermittent fasting, tirzeptide, and workouts twice a week I have only lost 5 lbs in months.
If you're combining a ketogenic diet AND intermittent fasting AND a GLP-1 inhibitor AND exercise and you're still losing less weight than observed in the Ozempic studies, it's likely that there's more to this story.
Ketogenic dieting does not automatically translate to weight loss. Keto simply makes it easier to reduce caloric intake. It's actually very easy to gain weight on a keto diet due to the high caloric density of consuming that much fat.
> Now I begin to feel incredibly depressed, I can't sleep nor focus.
Honestly if you're having these dramatic negative effects from minor caloric restriction with GLP-1 inhibitors, something else is going on.
"if you eat according to this plan and make sure to get 8 hours of sleep a day, you won't even feel the cravings"
Is stuff that fat people say. They totally buy into it and buy all of the products to help them convince themselves this is true. Then they get disillusioned when it doesn't work, have a crisis of faith, then go to the next fad to get over the self-hatred caused by their failure at sticking to something so easy.
Intermittent fasting is great. It got me from 225 to 165, kept it off for the past few years with no effort (my entire metabolism recalibrated to 165-175, I guess.) I also know people who cry actual tears when they're very late for a meal, or panic. Those people need therapy and/or maybe an injection to artificially lower their appetites to the level where I also artificially lowered my own appetite.
Intermittent fasting is no more natural than injections. Dieting is modernity.
I’m certain IF more closely resembles how humans ate for millions of years, not knowing when our next meal would come before becoming an agrarian society, and we haven’t had much time to evolve since then.
So, yeah, dieting is modern, but so is an abundance of food. Both are equally unnatural.
> Many people (will only speak to America), view being fat as a literal moral failing. Gluttony or overeating are not the sin, but being fat.
As an American with a sister with thyroid issues, I can say that is absolutely not true for the majority of Americans. People are mostly sympathetic to those who are not obvious slobs.
How would you even know the cause of obesity of a stranger?
This is why viewing being fat as a moral failing is mistake regardless of the cause.
I'm pretty sure a lot of people view your sister the same way just because they have no idea she has thyroid issues
People are mostly sympathetic when it's physical issues. Psychological issues are treated as diseases of the soul that you only need God or willpower or whatever to fix. And most fat people are fat because of the incentives in our society, but admitting that also goes against certain political ideologies...
It's not that there are incentives for you to be fat, but there are incentives for things which happen to cause you to be fat.
The car industry is a huge one. Making people drive everywhere means more car sales, more fuel sales, more infrastructure built for more cars. And it also makes you fat as a side effect.
At a low level, yes, corn, but at a high level: more consumption = more money.
Everyone benefits from you being fat. Your doctors, your car manufacturer, food manufacturers, everyone. Except maybe health insurance. But they're not hurt too too much.
There is no doctor on Earth who goes to work and thinks "thank god for fat people or I wouldn't have a business".
There's plenty of doctors and surgeons who wish there were less fat people, because they enormously complicate doing surgery on and managing in hospitals.
> There is no doctor on Earth who goes to work and thinks "thank god for fat people or I wouldn't have a business".
I agree, but this isn't how incentives work.
Ultimately, there are billions of dollars at play here that rely directly on obesity. The mechanisms of the market and human behavior transcend moral judgement.
With respect, neither of you are qualified to speak for majority of Americans, but given the amount of effort, money, ink, and television dedicated to looking better and losing weight combined with the fact that there's even a thing called fat phobic that even requires definition just to push back on all that...
I think there's sufficient reason to believe that "Overweight = bad" is a common standard that at least people hold themselves to.
We must live on different timelines. Pre ozempic America was the proudest nation of fat people I have ever encountered (excluding the costal elites of course).
Third American here, and the push for fat acceptance was so little of my media consumption that it surprised me so many people spent so much time and energy on the topic.
I agree with this take but want to add that once everyone is doing it, these opinions will change drastically and everyone will pretend like they were never against it.
Another interesting question is where do people go from there? What is the next signal of virtue, I wonder.
You can be gluttonous and still thin. I eat 2 lbs of ground beef a day, with tons of cheese on it. For breakfast I have 6-8 eggs, with cheese. I have my morning coffee with heavy whipping cream. For desert, I whip up some of the heaving whipping cream and have it with frozen berries thawed out.
It drives gfs nuts but they're too anti fat to try it.
That’s a horrifying amount of saturated fat per day, though. This is an extreme risk for heart disease.
I keep hearing this, yet after 13 years of keto my cholesterol is still 100. Being fat is much higher-risk than eating fat.
I'm all for obese people taking Ozempic if they really need it, as well as thoroughly studying its long-term benefits and risks, but the fact that we're at the point of considering medical intervention as the population-wide solution to obesity is an abject failure of policy. Looking at our nutritional guidelines, you'd think everyone in America was an extreme athlete. All we have to do is:
1. Take something like the food pyramid, and put vegetables on the bottom, put fat/dairy/coconut and protein/meat/eggs/soy/mycelium in the next level up, put fruit in the next level up, and put starches and sugars on top. In other words: eat real food, mostly plants, without extreme high-carb macros, and treat fruits as dessert. Reverse the failed policy of demonizing saturated fat, and make this the official dietary recommendations for at least a generation.
2. Provide an incentive structure to use lower-GI ingredients in food products. For example, largely replace sugar with inulin fiber sweetened with stevia and/or monk fruit, and largely replace flour with alternatives made from blends of flax, wheat gluten, and resistant starch; no one will notice the difference. Stop letting Cheerios of all things market itself as "heart healthy", at least with its current formulation.
In this world, people would eat way more veggies because they'd grow up with parents and restaurants preparing them properly (with saturated fat and salt). Even for those who didn't, high fiber fortification of UPFs would provide a reasonable backstop. The low-fat/low-salt era's reframing of healthy food as "bland" is a crime against humanity.
For any fat people we still have after that, sure, put them all on Ozempic. It just shouldn't be the expected default that unmedicated people are fat while the medical establishment shrugs its shoulders and doubles down on half a century of empirically bad advice.
I'm not a Catholic, but wasn't the idea of an indulgence that God intentionally allowed an alternative path to redemption, such that if you buy an indulgence, you are (at least by their definition) worthy and deserving?
I always thought of this as essentially the same idea as with Civ allowing you different paths to victory.
I thought Martin Luther's issue was more with the organization selling indulgences than the undeserving buying them. He preached justification by faith alone. Not some org selling justification.
Yes indulgences mean something different in Catholicism, they remit the "temporal effects" of Sin ie its spiritual consequences but don't "forgive" it like "Sacrament of Reconciliation" would..
I think that parent is perhaps confusing it with the sin of Gluttony.
The weight loss mechanism largely just comes from suppressing appetite though, so it still lines up with the penance for sin narrative. It’s not that different from wearing a hair-shirt and whipping yourself if you find yourself having lustful thoughts. Only instead of a whip you just feel kind of uncomfortable and nauseous if you eat too much.
I'd describe the effects as basically the opposite of self-torture. Self-torture is dieting/fasting without the drugs. With them, it's great. No afternoon light-headedness and difficulty concentrating, no hunger pangs, no "hangry" effect, no cravings you have to keep suppressing. Just smooth sailing. (though experiences do seem to vary—as do dosage levels)
That's true of semaglutide, but newer peptides like tirzepatide (a dual-agonist) and retatrutide (a triple agonist) have additional effects like improving insulin sensitivity, and simultaneously slowing the release of glucagon and activating glucagon receptors, which directly increases fat oxidation and thermogenesis.
my estimate would bigger than others and I would put it at 30-50years.
I take smoking as a cautionary tale, in the beginning it was pushed as not just a recreational thing but a healthy activity that bring benefits with papers published to sing praises about it. my parents were even nudged by their teachers/doctors/etc when they were young to try smoking.
now we all know that smoking is beyond bad and all that early "research" was just people paid off by big companies to promote it.
> I take smoking as a cautionary tale, in the beginning it was pushed as not just a recreational thing but a healthy activity
While i agree the gist of what you are saying, also important to mention that humans started cultivating tobaco when mamoths still roamed the Earth. There was indeed a concentrated pro-smoking publicity campaign by tobaco manufacturers in the 1930s, but it was hardly “in the beginning” of our tobaco use.
I think a lot of people share similar concerns, but the benefits of a successfully therapy are so extreme it would take quite a lot to derail ozempic. People easily gain 5 or more years of lifespan by not being obese, avoid myriad related health conditions, and are truly much better off. It would take a lot to reduce someone's life expectancy by a comparable amount and we haven't seen that much besides gastrointestinal issues.
We performed the surgical options like stomach reduction before this which come with serious danger for comparison
Under-discussed benefit: being able to have all your clothes actually fit at the same time (no wardrobe scattered between your "skinny" weight and your "fat" weight and rarely being in the right place for more than a handful of pieces to fit entirely correctly) so you can spend up a little on nicer clothes without worrying you'll only be able to wear them part of the time. Worst case, you start to pack on a little too much and they start getting tight, you increase the dose or go back on the drugs for a week or three (or just do it the old fashioned way—hey, it works some of the time, temporarily) and ta-da, right back where you want to be—you're not going to pack on weight and find yourself unable to lose, so buying "skinny clothes" isn't mortgaged against your future success at forcing yourself to eat less.
Ozempic itself has been in use for almost a decade now (originally approved for type 2 diabetes in 2017). Many millions of people have taken it, without much in the way of serious complication.
Exenatide had been in use since about 2005, and by 2019 had more than a million people on it. Some of those patients have literally been on it for 20 years. It does have a worse side-effect profile than Ozempic (or the more modern GLP-1's like zepbound), but even then the benefits outweigh the risk for those diabetics.
Today it is hard to argue the benefits of modern GLP-1s don't outweigh their risks. They've been extensively tested, the class of drug has been around for decades, and they are used by many millions of people.
I personally lost 120 pounds on Zepbound in a little less than a year. It's been life changing, and anyone who thinks I might be less healthy now is very clearly wrong. Literally every aspect of my life has been greatly improved.
There’s two sides to that coin. Obesity has known long term harms. So what we are looking for in a deal breaker can’t be a small but statistically significant increase in some cancer or other. We’d need something as bad as smoking to outweigh the benefits.
> Gluttony or overeating are not the sin, but being fat.
This is a strange thing to say. If you do something normal, and you end up in a normal state, why would that be a moral failing? There's no such thing as "overeating". Different people eat different amounts. The same person eats different amounts at different times.
> (From that perspective:)a miracle cure that allows someone to stop being fat is like an indulgence (in the Roman Catholic sense). It’s a cheat, a shortcut that allows the unworthy to reach a state they do not deserve.
This is incoherent. If you believe that being fat is a sin, but that the things you do that make you fat are not sins, then a miracle cure that makes you thin removes the only sin you were committing. You can't be unworthy if you're not fat. In order for a miracle cure to be "cheating", it is necessary that the sin is in the behavior and not the result.
> I find it fascinating how much a pretty large group of people just hate semaglutides and seemingly need to believe that it's some kind of Faustian bargain.
There have been some scandals about "miracle drugs" which bad effects have been found only years after being on the market. And side effects can be crazy: I use D2 agonists which works wonder to handle a prolactinoma (like shrinking a tumor with a simple pill every 2 weeks wonder), side effects of this kind of medication can be different addictions (sex, gambling, purchasing etc.) which is always fun when you're one in a thousands to get it.
You've got a crowd of people raised in a Calvinist society who think nothing good comes without suffering, you've got people who feel this is a cheat where discipline should win out, and you have a bunch of people who are used to all easy solutions coming with either a bad lottery ticket or externalities on other people/the environment.
They can all agree that they're waiting for the other shoe to drop.
That said, we are at a point where people are overweight enough that getting exercise has its own risks, and taking a medication that allows you to be more active is likely to cancel out some of those downsides. As long as you do both I have no problem with people taking ozempic, mounjaro, etc.
I would prefer if we figured out what other than cultural changes is making everyone have symptoms of inflammatory dysfunctions. There is more than one thing going on. Processed foods, contamination, some microbe that doesn't culture in agar. And it's spreading to more of the world.
> Calvinist society who think nothing good comes without suffering
Or, some of us older folks have been around long enough to understand that we are, in an uncontroversial and factual way, the long term medical trial, and long term effects found in that trial, along with the eventual market withdrawal, may not show up until 10 to 20 years later, creating a healthy distrust in the money/corporations behind the, sometimes outright crafted [1], early medical trials.
How many times has a drug had negative effects that only showed up after 10-20 years? Out of all the drugs that have been widely prescribed in, say, the last 100 years? And it’s not even actually a new drug class - Liraglutide was approved in 2010! Should we wait until the clinical trial participants all die of old age until we put a drug on the market?
Most the nonpharmaceuticals I could list from memory, I had to google the medication
Nonpharmaceuticals
- microplastics
- bisphenol A
- asbestos
- nicotine
- DDT
- fungicides like HCB
- PFAS
Pharmaceutical
- benzodiazepines
- Terfenadine
- Benfluorex
Of the 528 new drugs approved over the period of interest, a total of 22 (4.2%) were eventually withdrawn. Between 3.9% and 4.4% of the drugs approved in each 5-year period were eventually withdrawn (χ2 = 0.04, p = 0.99 for difference among 5-year periods). The median time between approval and withdrawal was 1271 days (interquartile range 706–2876).[0]
By some estimates 7% of US have used semaglutides. That is 24.5M people. That could be 24.5M people who have benefitted but if it turns out that there are long term consequences, that's a lot of people who are now all in that ship together when at least some of those users could have chosen lifestyle intervention rather than chemical intervention. If we take the 4.2% recall rate that gives an EV of 980k people in the US who will suffer adverse effects from semaglutides
I wasn’t talking about non-pharmaceuticals, and neither were you. Non-pharmaceuticals don’t go through clinical trials, and they mostly don’t require any pre-approval. So that’s clearly just trying to pad your list.
Benzodiazepines do not have effects that only suddenly show up after 10-20 years of use. The serious side effects/withdrawal show up with a few months of heavy use, sometimes sooner. They’re also actively prescribed (with some appropriate caution), so a really weird one to lead with.
There are actually quite a few drugs still widely prescribed today that cause similar QT prolongation to terfenadine (e.g. quetiapine). The difference is they are for more serious conditions where the other options have similarly serious side effects, and terfenadine has to compete with Benadryl. No reason to have to get periodic EKGs just to keep your sinuses decongested in allergy season.
> Of the 528 new drugs approved over the period of interest, a total of 22 (4.2%) were eventually withdrawn. Between 3.9% and 4.4% of the drugs approved in each 5-year period were eventually withdrawn (χ2 = 0.04, p = 0.99 for difference among 5-year periods). The median time between approval and withdrawal was 1271 days (interquartile range 706–2876).[0]
I’ll give you the benefit of the doubt, and assume that you just didn’t care to read the paper once you assumed it agreed with you and did not selectively quote on purpose. From the same paper:
> Of the 22 drugs withdrawn, 11 first had a serious safety warning and 11 did not (Table 2). The median time between the Notice of Compliance and withdrawal was 1271 days (interquartile range 706–2876).
So, the percentage you quoted was double what we were actually talking about here. On top of that, I don’t think you finished reading what you did quote; the median time to withdrawal was < 5 years, and if you actually look at the table only two drugs with serious safety issues actually hit the 10-20 year range you mentioned.
> those users could have chosen lifestyle intervention
We’ve been trying all kinds of “lifestyle interventions” for a long time, from doctors telling people to exercise to semi-organized campaigns of body shaming. It hasn’t worked for the vast majority of people in practice. So unless you have some actually novel idea here, you’re essentially trying to get people to switch from a drug that works to the power of positive thinking. Good luck with that.
It took us 10-20 years to find out about tardive dyskinesia due to antipsychotic medications and the long term dependency and withdrawal effects of benzodiazepines. Two entire classes of drugs that are now in common use, so it’s not unheard of.
I’m not saying we should take Ozempic off the market but don’t be fooled into thinking that we’re immune to unintended consequences just because we did a few studies (almost all of which were on diabetics with controlled diets).
At no point did I say we were immune to unintended consequences. Just that demanding every drug be used for 30+ years before you’ll touch it is not actually making an analysis of the tradeoffs involved.
Also, the drug classes you listed are not great examples. Benzodiazepines don’t fit what we’re talking about at all: it’s common to develop tolerance and get serious withdrawal symptoms from a few months of heavy use. You definitely don’t need to take them for 10-20 years (or even the 8 years since Ozempic was approved) to notice the serious side effects. If Ozempic killed you if you quit it cold turkey, we would already know. Psychiatrists were not unaware of what happened when you took too much Valium back in the 60s when it was first introduced. It’s just that they (and society in general) had an attitude toward risks that is totally alien to modern sensibilities (and to be clear, I think it was bad).
First-generation antipsychotic’s incidence of TD was strongly correlated with dose, which was strongly correlated with having schizophrenia and other mental illnesses involving psychosis specifically (as opposed to other indications like bipolar without psychotic features or major depression). Getting TD later in life but being able to live outside of an asylum (they were still around when first-generation antipsychotics were commonly prescribed) is probably a tradeoff many of these people would have taken, even if they knew about it.
> I would prefer if we figured out what other than cultural changes is making everyone have symptoms of inflammatory dysfunctions.
I personally hope it's just cultural and sugar/hfcs. Because some alternatives might be grim to reckon with just from a humanistic/grief perspective: https://pubmed.ncbi.nlm.nih.gov/34484127/
You've also got the crowd who would argue that there's nothing wrong with being fat in the first place and that are scared of society pressing on this matter again after years of pushback.
As someone who was 100 pounds overweight for a long time, and now isn't, that mindset is really dangerous and preventing a lot of people from living life to its fullest.
There is never any reason to be cruel or unkind to people who are overweight, but pretending that it doesn't have negative consequences or is even "healthy for me" or whatever is really harmful.
I think there is a large chance that this crowd referenced arguing for "this" is even smaller than than the population of (25? 50?) trans ncaaa athletes that all the rubes believed was ruining america. Loudmouths on the internet exist and suck but don't represent everyone.
> That said, we are at a point where people are overweight enough that getting exercise has its own risks, and taking a medication that allows you to be more active is likely to cancel out some of those downsides.
And yet we rarely ask or say "maybe I should just eat fewer calories?" Unless you have some other disorder that prevents normal bodily function, that does work (and would be viable I'd imagine for the majority of people being prescribed).
But it requires patience and discipline which are basically non-existent for the majority of the population.
I studied chemistry at university and my master's was in medicinal chemistry.
My main takeaway was that "chemicals = bad" is a better heuristic for a starting point where you then look for exceptions or accept them as the last resort after exhausting other options.
Would you let AI loose on the software of your airplanes or nuclear power plants? Medicine is like a sensible idea that should be ok but is hard to rein in and localise to just the area of effect, we hope that it only makes the change we ask from it but we ultimately can't really say with certainty that it isn't also doing something else
I'm actually generally more surprised that people are so trusting of taking medicines and pop pills like they're candy
I think you've got to the nub of it. I worry about e.g. gall stones risk in 10y. But, friends worry it shows a lack of moral fibre or something. They aren't the same kind of worry. One is paranoia about past drug emerging issues and the other is tied up in belief eg poor addicts own their own fate, fat people should htf and eat less, depression isn't real... it's usually a short path to "I don't want to have socialised medicine for poor and old people"
The drug companies are very good at making new drugs with high profit potential look better than they are. I'm worried semaglutides are another fen-phen, Vioxx, Quaaludes, Trovafloxacin or OxyContin.
One thing to watch for is effect size: how big of an anti-aging effect does Ozempic confer relative to other good interventions? Were the subjects doing other solid anti-aging interventions like the Fasting Mimicking Diet (FMD)? If not, the 2 interventions might affect the same pathways with the result that if you are doing FMD, you get no additional benefit from Ozempic.
Fen-phen is particularly interesting here because people reported that not only did it help them lose weight, it gave them more willpower and changed their personalities for the better.
Don't worry, GLP1 RAs are nothing like those other drugs. In fact I'd really challenge you to examine even one of the correlations there, the scale of research, use, known side effects, effectiveness is completely different.
The idea that people might only benefit from something like Ozempic a little if they were doing some other intervention before is irrelevant, because no one is doing those other interventions. Requiring people to suffer before providing useful, known-safe and well-researched medication is silly.
I think that's a completely reasonable concern to have, it doesn't seem to be the case wrt obesity but for the myriad of other potential effects it's important to keep in mind.
I'm not even ready to concede that it is a good weight-loss drug -- but then I haven't really investigated much, so I'm just repeating what I heard from researcher Ben Bikman and maybe other researchers. I heard that most people choose to discontinue it after 4 or 5 years or less, regain most or all of the weight, then refuse to go back on it.
I've been on Zepbound for ~25 weeks now and one of the first things my doctor told me was that this was a lifetime drug. He pointed out that I had a choice, of lifetime drugs. I needed to do something to get my cholesterol under control. That meant start statins now and likely add blood pressure meds and diabetes meds in the next 2-5 years. Alternatively I could start Zepbound, which would likely address all 3 and result in better quality of life in the next year. So far it seems like it is doing exactly that.
I'm sure some people are going into this without that knowledge, but people are being told this is a lifetime commitment. What you don't see a lot of is why people stop taking it. There's some cases of people losing and then stopping, but the majority are because insurance is forcing people off of it. Just look at the recent CVS Caremark forced switch from Zepbound (2nd Gen) to Wegovy (1st Gen) in July.
I'm fairly certain that literally every doctor tells literally every patient this. Mine sure did. It's also on the handout your pharmacy gives you, the website for the drug, and in fine print at the bottom of most commercials.
Nobody expects a single does of ibuprofen to cure your headaches for life. Similarly, this doesn't "fix" your biochemistry for life, you have to take it in order for it to work.
> I suspect that this info is intentionally down-played so that it doesn't affect sales.
Yea, hard to figure out why drug companies keep producing "Faustian bargains" in our current system. What galls me is people assume the best for new drugs instead of forcing the _for profit_ entity to prove it's actually safe and useful.
To the extent that, reliably, the first comment on these posts on Hacker News are some wishy washy anecdotal emotional blackmail garbage that completely obfuscates the point and runs direct interference for these large profitable organizations.
To the extent that it's hard to believe that these posts even on this tiny corner of the internet aren't bought and paid for. We live in a society that cherishes organized crime and denigrates hard work. I would not look forward to "new drugs" in this regime.
Novo Nordisk Foundation is a nonprofit but Novi Nordisk the pharmaceutical company is very much a for profit entity - it’s publicly traded on several stock exchanges including the NYSE. The foundation owns most of the voting shares but only about a quarter of all outstanding shares.
I've read (anecdotes from people in the fitness/body-building space) that the default dosing could be too high for many people. And the side-effects seem to ramp up with the dose.
IE, if you're getting weight loss at 1/2 the default dose, you might want to stay there, even if your MD wants you to increase to the default.
[default uses loosely here - people build up from a low dose over the span of weeks/months]
And the weight gain is due to a lack of lifestyle change. The drug just numbs your appetite, so you don't eat as much. If you go off the drug and return to over-eating, yep, you gain the weight back.
I also suspect many people lose the weight too fast and go too far. "Ozempic butt" is a joke for a reason - people loose a bunch of fat, but the massive calorie deficit also means they aren't exercising (no energy, and they probably weren't before the drug either), so they've probably crashed their metabolism.
I tried it. I started down about 80 lbs from my heaviest, but a good 40 lbs from ideal/20 lb from healthy weight.
The first time I tried it I followed dosing guidelines for ramp up; side effects were horrible, didn’t lose much weight, and it just kept getting worse.
Second time, after a few months off, I started at lowest dose and stayed there. Side effects were better to start but ramped up again. Eventually my digestion stopped entirely and I couldn’t eat without pain; that actually was good for weight loss but very unhealthy (e.g. despite being hungry and lightheaded the pain kept me from eating more than 400 calories). Eventually it passed but I couldn’t justify taking it after that.
Basic side effects: exercise intolerance (higher starting rate, much faster increase exertion, chest pain after ~150bpm when previously I could run nearly an hour and go up past 180 without issue), fatigue in the morning (despite essentially maintaining my pre-ozempic nutrition), significant increase in resting heart rate, significant decrease in HRV, and digestive upset (basically alternating diarrhea and constipation).
Many of these side effects are well known, others less so.
Ozempic, when micro dosed, did help reduce hunger and make a weight loss diet easier to sustain, until the side effects got so bad I wanted to comfort eat. But mindfulness and healthy lifestyle are similarly effective without crippling side effects.
Try Zepbound. You lose more weight with far fewer side effects.
Although, you may still have issues. It does just sound like there's something unique about your chemistry. I don't think that many of those side effects are even in the ballpark of normal.
I would like to try it, but I don’t think it is available from shady internet doctors and insurance won’t cover it because I’m not diabetic. Shady internet ozempic passes the cost-benefit test (barely, considering I can successfully lose weight without it it’s just hard). Full cost out of pocket it does not. Maybe in a few years.
I would worry that the side effects I care about are not the side effects that others report being improved on zepbound.
Protip: Get an ultrasound on your liver. Almost every obese person has (what used to be called) fatty liver, and that's usually enough to justify the prescription to your insurance company.
Have you looked into Tirzepatide? Basically a combo of ozemspic plus a GIP drug. Again, anecdotes from bro-science, but appears to allow lower dosing and reduced side-effects.
Very much the default is too high and the bro-science was indeed early on this. I’m super sensitive and had the bad negative reactions at 1/10th the starting dose. It’s been a wonder drug for me though, finally able to put my life back together after ME/CFS all but destroyed it.
Just about every single adult woman in my wife's extended family is on Ozempic. None of them are obese at all. Or diabetic. They are all using it to "lose a few pounds" (we're talking like less than 20 pounds; Yes, as you might expect, there are some unrealistic beauty/success standards in my wife's family). So I think there are a lot of people who are annoyed by that, because of the message it sends to completely healthy-weight girls/young women who don't look like professional super models in a swimsuit.
Since we have young daughters, that aspect of Ozempic really bothers my wife. Though she would have no issue with obese/diabetic people using it to get healthy.
Personally I do think it is a miracle drug and I'm glad people are getting healthy because of it.
To be fair, if you're an average height american woman (5'4"), the nominally healthy BMI range is just 37 pounds wide from 108 to 145 pounds, so 20 pounds can be pretty significant.
I fall into the same category as your wife's extended family. I used it to get to the weight I feel most comfortable and I've gone back on it periodically (like after 5 weeks of work travel) to get back within 5 lbs of that weight (where I can manage the additional weight loss on my own).
When being fat becomes more of a deliberate choice (due to the drug accessibility) I do wonder how society and society's expectations Will change. Will women be even more pressured to "bounce back" during postpartum? Will the "baby fat" we only get to have during adolescence be eliminated and drop out of the shared experience of growing up?
There's also a lot of concern within the eating disorder community about the potential for abuse, because these drugs are so easy to get a hold of by lying on telehealth (could be argued that I've abused them by getting them when they're not truly necessary).
It's a tool, like anti antidepressants. When used right and in the good settings they can be amazing, when used as a magical pill without treating the underlying issues and not understanding its mechanism of action you're in trouble.
I know people who used anti depressants for a few weeks, while going to therapy and fixing their shit, they were out of trouble in less than 6 months. But I also know people who've been basically been taking pills for their entire adult life with absolutely no sign of getting better, the pills just make them cope slightly with their shitty routine/job/&c. while completely destroying their body and making them numb to everything. Same for ozempic, I know people who think you just swallow the pill and that's it, they still have horrendous diets, drink 800cal stabucks "coffee", snacks on sweets all day long, and they're actually gaining weight...
Another good example would be sleeping pills, take them once a year to fix your jetlag and they're amazing. Take them for 10 years because you can't fix your routineof watching tv shows in bed until 1am and "need" pills to fall asleep quickly, you'll just fuck up your circadian rhythm for good and it'll be 10 times harder to get out of the cycle
If you truly want to fix your shit virtually any tool is good, but if you just want a magic pill without putting any work you're doomed, the main issue is that it's advertised and sold as a magic pill
There were even people who felt this way about anesthesia too. To survive in that era, they had to believe that suffering was somehow good for healing (or at least good spiritually) and talked about anesthesia as if it were cheating the natural god-given order.
I think this might be revisionism. A lot of people feared early anesthesia because it was far more dangerous than today.
I also notice people will make note that 'eccentrics' from the 1940s-1950s hated air conditioning but it helps to understand it was a dangerous technology that regularly injured and killed people back then, especially in its earlier days the adults of that period were children during. AC didn't get safe until fairly recently in the 70s, 80s and 90s. It would catch fire or leak poison that killed people in their sleep. Some people just saw it as an unnecessary risk. Same with early fridges. When they leaked, that leak could be fatal as poison or explosion.
It wasnt until later that these technologies got safer and even now today, we consider full anesthesia a last resort and will always try to get away with local or twilight anesthesia because full anesthesia does regularly injure, disable, and kill people. Evolution didnt design us to be trivially "shut off" like this. Injecting us with substances like that will always come with risk.
In other words, a lot of those people weren't mindless luddites, but people who assessed their personal risk and said "nope, not worth it." I think that's perfectly fine.
I'd argue the revisionism of today and the ego justifications of the time were just that, ego protection. Its far easier to say "Well, I'm tough, I don't need that," then "I'm scared of that." The former is rewarded in our individualist capitalist society. The latter is vulnerability and honestly which is often only punished in a society like ours. We see it today with people with limited access and affordability to healthcare in the USA putting off care or engaging in various home remedies, alt-medicine, supplements, or conspiracy-culture-esque pharma drugs gotten cheaply via the gray market.
I see a similar hesitancy around anti-alcohol addition treatments like naltrexone. People almost _want_ it to be difficult to quit (or lose weight), like there should be some moral struggle associated with it
Alcoholism is a moral failing, and the struggle and punishment are real, and come not only from outside, but also from within.
One can try to rationally argue their way out of alcoholism being a moral failing, but then one notices that in a similar way they can “whitewash” any other moral failing, and the words lose their meaning completely.
Yet people use these words to mean something, and abuse of alcohol falls under that meaning, and every society in existence has always cautioned against and condemned it.
I think there's a justifiable fear/dread when things that used to demonstrate virtues no longer do so.
For instance, being in shape used to (usually) demonstrate discipline. Art or music used to demonstrate attention to craft and practice. Knowledge demonstrated time devoted to study.
This isn't to say that the world is worse with these advances (I'd be hopeless without search engines, and I am grateful that people get to live longer and healthier with semaglutide), but I think a little bit of mourning is understandable: what used to be the fruits of hard work are now a dime-a-dozen commodity.
Was waiting to see this comparison. Glad to see that meritocracy is becoming the pejorative it was always meant to be. Meritocrats are unironically bigots.
> I know many talented engineers who hate AI coding.
People whos primary skill is coding, hate AI coding. No talented engineer hates AI coding. The distinction is this: a coder knows how to use their tools, an engineer knows how to work with people, understands product, process, users, and knows how to use their tools.
Talented engineers hate the HYPE around AI. And those of us old enough to remember sigh and think "This is just dreamweaver all over again". It is ESB's with "drag and drop" workflow tools. AI is just another useful tool that a good engineer can pick up and put down where appropriate.
As a talented engineer, I hate AI coding because it doesn't do what it says on the tin. If GLPs made people hallucinate weight loss that wasn't actually happening, I'd be angry about them too.
I’m in the cautiously optimistic camp. I’ve seen two people puke their guts out the day of their doses, but nausea isn’t so bad compared to the health consequences of being overweight.
Some studies have shown people just drop back to their old habits when they stop, and that long-term use isn't good (pancreas, kidneys, etc). It's life changing for some, but like any medication, it shouldn't be used casually.
I'm not a fan because it's expensive and once you go off of the drug the weight comes back on (at least from what I've read). That's not a trade-off I want to take lightly.
There's also something to be said for gaining the discipline to do it yourself along the way, which may lead to keeping more of the weight off in the long run.
We also don't know what the long term side effects of it will be, if any.
I don't find any of that unreasonable to me. I'm saying this as a type-2 diabetic who could stand to lose a lot of weight.
> I'm not a fan because it's expensive and once you go off of the drug the weight comes back on (at least from what I've read). That's not a trade-off I want to take lightly.
The rest of the incorrect points other people have basically covered, so won't repeat.
Is teaching the discipline lesson worth the shorter life people would live without this medication? Maybe we could find another way to teach people discipline that doesn't maintain a threat to their health?
> I don't find any of that unreasonable to me. I'm saying this as a type-2 diabetic who could stand to lose a lot of weight.
Gonna be incredibly blunt, but talk to your doctor and get on GLP1s. Take a low dose if you want.
GLP1s are incredibly well researched and effective. Imagine dying of a heart attack early because you refused to properly research effective, low-risk medication that is being used by millions and recommended by professional organizations and doctors widely. Real Steve Jobs energy.
> We also don't know what the long term side effects of it will be, if any.
The first GLP‑1 receptor agonist was commercially released in April 2005, meaning 20+ years. People who often repeat this: If 20-years, and tens of trials, isn't long enough to "know" then where is the line exactly?
Thalidomide by contrast was available for 4-years, Vioxx for 5-years, and Rezulin for 3-years by contrast.
> There's also something to be said for gaining the discipline to do it yourself along the way, which may lead to keeping more of the weight off in the long run.
That doesn't work; we know it doesn't work both from small and large scale studies, and population evidence since 1970s. So you're promoting the same thing we've been doing, and failing at, for beyond all of my lifetime. Feels like a religious belief at this point, rather than following the data and what we know from it (i.e. that objectively does not work, and has never worked).
Is there something new you know that health experts haven't known as Obesity as increase up through 40.3%+ (with overweight being 73.6%+)?
"Discipline" doesn't exist, or rather it's a feature of your brain and not something you can necessarily learn. GLP-1 inhibitors and stimulants (modafinil, amphetamine, etc) are drugs that literally give you "discipline".
Habits are something you can learn though, and having more discipline helps you form them.
Well, considering that the drug was originally developed not for weight loss but for type 2 diabetes management, it's not terribly radical to be skeptical or outright dismissive of it as some miracle weight loss drug (even if that is a consistent side-effect).
The whole rush to get people on the thing feels like an opportunistic pharma grab (because it is). The outcome of those sorts of things is never in favor of the individual or their well being.
I agree, and I am a consumer of those myself, which did absolute wonders. And of course I will assign vastly more weight to my own experience, than to the opinion of some random guy on the internet who only read about it.
However, we also need to be conscious that this is a very very big business, and given the size of the market, is happy to pour billions into some studies that will demonstrate that it has all the benefits in the world and cures everything. Addressing obesity is a humongous benefit in itself, and helps with all the medical conditions that result from it (which in balance makes most mild side effects irrelevant). I am a lot more skeptical about those dozens of claims that it improves X by Y% (often low single digit). Most medical studies in general are dodgy, show minor benefits on small samples in a massively multivariate environment, which more often than not are statistical noise carefully selected, when the approach don't have outright flaws or fraud.
> find it fascinating how much a pretty large group of people just hate semaglutides and seemingly need to believe that it's some kind of Faustian bargain.
Its just inductive reasoning. Most things are not free, let alone miracles. Nearly everything in life has a cost.
There are people who are going to hate anything like that, because it makes a very difficult task (losing weight) significantly easier. And we hate it when the damned kids, what, with their Tok-Clock and deadass rizz, have it easier than we did back in the day.
That being said, the fact that we let our society in North America get to the point where something like semaglutides are such a huge deal is something to honestly hate, and I think some of the misdirected hate is really a hatred for that.
I think Ozempic is just a symbol of what modern life looks like. Obesity is a problem that 100% could be solved with a cultural shift (see Japan), but instead we decide to use medicine. It's like, humanity at large grew such big brains because there was evolutionary pressure to be intelligent, but now we're using intelligence to remove that pressure. Which would make sense if we redirected that intelligence to something else, but we don't.
I think the reason why we don't see aliens is that intelligent life isn't sustainable long-term, and there's a long list of reasons why intelligence leads to self-destruction.
Sure, a lot of problems could be solved with a cultural shift, but most people are in a rat race to survive
And those in politics are not interested in change since because (the cynical part starts here) they are selected / sponsored by billionaires who own the media, or go to politics as a job and not to help anyone but themselves
On a side note storing fat to feed the brain in case of bad times makes sense. In the past there were no convinience stores, nor refridgerators
I am one of those people to some extent. For me, it's the naturalistic fallacy I can't get over. I drink caffeine daily, but the idea of hijacking my hunger with an injectable induces dread. I would like to believe that there are no long-term side effects, but:
1. We have to trust the data of for-profit pharmaceutical companies and their trials. They are incentivized to produce optimistic results.
2. It's relatively new (insofar that a lot of people are taking it). Opiates were touted in a similar way until the other shoe dropped. There exists an undefined line in time where I would feel more comfortable.
3. It is/was made of a poison from an animal.
4. The extreme benefits are overwhelmingly in obese candidates. Keto is the same way; I tried it and it was not for me because I am not obese.
I'm actually open to any sort of evidence that will change my mind. No name calling please.
> I find it fascinating how much a pretty large group of people just hate semaglutides and seemingly need to believe that it's some kind of Faustian bargain.
Some of us also remember previous weight loss drugs which had similar levels of hype and later got pulled because of really bad side effects.
If I needed to lose 100+ pounds, I'd be at my doctor tomorrow asking for it. The side effects of 100+ pounds are way worse than anything semaglutide might cause.
For people who are using it to lose 10-20 pounds, the tradeoff isn't as clear.
I am cautiously optimistic and hope that semaglutide lives up to the hype. lots of people will benefit if it does.
Apologies if this sounds argumentative but I would be super curious of the cross-section of people that are pro-semaglutides and also anti-vaccine. I am fascinated by that too! (And I trust that HN will share a lot of great datapoints)
>seemingly need to believe that it's some kind of Faustian bargain
I mean, that's because that's literally what they need to believe. A majority of people has been brought up on an incredibly moralized account of human behavior, and if it turns out you can just pour some GLP-1 drugs into the drinking water and basically fix a whole bunch of issues it will become obvious that a therapeutic framing is the appropriate way to look at these things.
For people who live in a world of vices and sinners who have to swear off the devil, this throws a pretty big wrench into the whole story, it's much more than just a drug.
I personally believe the theory that obesity in the US is caused by other things in the water supply[0], so adding GLP-1 inhibitors would cancel them out.
[0] obesity appears to be caused by moving downstream/to lower altitudes, and has increased in farm and lab animals at the same rates as humans.
I think it's a similar thing to those who are morally invested in human overpopulation and not consuming resources for climate change reasons and such.
The techno-optimist GLP analogs like solving these things with clean energy and other modern marvels throws a wrench into that story.
> every time in recorded human history when there's be a panacea or cure-all it's generally been snake-oil.
That's just not true at all. Like, not even close.
Almost everything we've invented in medicine has been free. As in, little to no downsides and just makes things better. And not just in medicine - look around you, compare it to 100 years ago. A lot of stuff is safer, for free.
Think about infant mortality. We went from 1/4 100 years ago to 1/1000s. For free. Surely birth must be more painful now, right? No... we got rid of the pain too. Well surely mothers die more, right? No... They die orders of magnitude less too. Well surely the Vitamin K shot must have SOME downside? Pretty much no, it just pevents bleeding out.
But usually when someone says panacea they don't actually mean a cure-all. Because, obviously, that's impossible and will always be so. They mean something with lots of uses and no downsides.
Wouldn't the side effects, combined by the accompanying lifestyle changes key to making this medication most effective, show its not a panacea or cure-all? The fact there are these second order effects with such incredible impacts would lead me to believe its more mechanistic than magical with how much obesity effects all sorts of body systems
also in the news in the last couple months was "promising for breast cancer" and another cancer (can't remember, don't care), and depression as well as some other mental health disorder.
If you would like to give me money i would be happy to do the research on what claims have been published about GLP-1 inhibitors since they became prescribed off-label.
I assure you it's more than "many conditions downstream of [...]", unless you want to concede that mental health like depression and dementia are related to gut bacteria, then we can be friends.
also, i caught wind that by December 2025 it's going to be recommended / "proven" to work for erectile dysfunction. At a certain point, we're mincing words.
As someone who saw miraculous cessation of lifelong immune issues on it, saw another friends dramatically improved allergy symptoms, another lifelong smoker finally quit, and other friends generally get in great shape, I actually do believe it’s uniquely good. If even half of the seeming benefits it seems to be showing in early stages right now turn out to be true, it is.
> I assure you it's more than "many conditions downstream of [...]", unless you want to concede that mental health like depression and dementia are related to gut bacteria, then we can be friends.
You have no way to assure that and haven't even made that assertion. Depression and dementia are absolutely related to digestion, gut bacteria (as you mentioned), metabolism, and hormones, all of which are affected by GLP-1s.
Also, if someone starts taking GLP-1's (which has a placebo effect to begin with), loses weight, exercises more, and sees improvement in their diabetes, why wouldn't they also see improvement in their depression?
This is specifically a study on people with HIV-associated lipohypertrophy, which is associated with accelerated aging. Not clear what this would mean for people generally.
Not really applicable in humans. Effect is smaller than in mice, and requires some pretty drastic restrictions that aren't exactly pleasant.
The thing with ozempic is that is seems to do several things, most (all?) of them good for us in different ways. We probably just lucked out. It's not the only case - plenty of drugs do incredibly good things with only reasonable side effects. Antibiotics. Ibuprofen. Aspirin. Vitamin D.
A recent example - statins used to be seen as a tradeoff: you get better cardiovascular health, but some hepatotoxicity. Nope, it was wrong - they actually protect your liver. I think the official change came out this year, when I started them a couple of years ago I still found it framed as a side effect.
People on ozempic certainly look more like the crypt keeper than a younger version of themselves. You lose all that buccal fat that defines your young adult face.
Or that's who you notice. My husband takes ozempic for type 2 diabetes and it completely fixed his blood sugar while causing very moderate weight loss.
What the people in this study have causes abnormal visceral fat accumulation in the belly and back and itself causes disturbing changes in body shape and appearance, does not respond or normal weight loss, and hasn't had real treatment options. That ozempic has beneficial effects for it in an RCT is actually awesome, it's the framing given by the headline that is bad.
Any means of attaining weight loss at a similar rate will tend to do the same thing. Especially if you’re starting from quite-heavy, not just dropping 20lb or something.
I notice it in people who have never been the weight that they're suddenly walking around as, with them it often looks overdone, too thin for their features etc, but in those who have used it to get back to weights where I've seen them before...I didn't guess. They had to tell me.
It varies. People are often thinner in their twenties than their thirties and forties. If you browse some before and after pictures the ones who have had their skin tighten tend to look younger for that reason alone.
This isn’t really surprising at all IMO, but it’s nice that it’s been confirmed.
> “The researchers believe semaglutide’s anti-aging properties stem from its effects on fat distribution and metabolic health. Excess fat around organs triggers the release of pro-aging molecules that alter DNA methylation in key aging-related genes. By reducing this harmful fat accumulation and preventing low-grade inflammation - both major drivers of epigenetic aging - semaglutide appears to create a more youthful biological environment.“
In other words, being medically obese ages your body quite a bit, its stresses out your body with inflammation, etc. Taking Ozempic helps people lose weight, which also reduces inflammation. This is sort of like saying we proved rain (usually) increases humidity lol. A very obvious finding.
The article even says “ Randy Seeley from the University of Michigan Medical SchoolView company profile expressed little surprise at the findings” :)
Yeah this is pretty much a nothingburger. I guess being fat causes biological damage similar to aging, and losing weight (which Ozempic helps with) reverses the process.
I think it's controversial mostly because it is mixed in with morality, self-image, personal freedom etc.
I think everyone has the right to be fat, if they have chosen to prioritise other aspects of life, but I think people should be informed and consider the "being fat can be healthy" movement to be quite disingenuous. Do what you want, but be realistic about it, and tricking people into ignoring the negative effects is not fair to them either.
Yeah it's clearly wrong, being fat is not healthy. There are multiple mechanistic explanations for why it might not be healthy (inflammation, hormones etc.), coupled with epidemiological evidence that obese people have massively higher rates of all sorts of health problems.
My bet is on the reduction in inflammation -- it's a notoriously beneficial positive side effect of GLP1 Receptor Agonists, along with the obvious reduction in weight or HbA1c.
Currently the only people experimenting with it are the underground gray market peptide enthusiasts (you can find them on reddit and elsewhere), but the results are quite intense.
[EDIT] Just to be clear, gray market Retatrutide is illegal, I'm not encouraging you to buy it or do even take GLP1s in general. The point is that we have a preview of anecdata from people (with obviously high risk tolerance) taking this drug.
> If Eli Lily is the only producer, how is the gray market being supplied? This makes no sense...
It turns out enterprising chemists and pharmacists are capable of reverse engineering.
I don't think it's that hard to figure out how someone might do it -- imagine having to reverse engineer food you've received, given many samples. Imagine some of those samples might have "fallen off the back of a truck".
> That being said, I'm waiting for oral GLP1 agonists. Injections are a hassle and gray market ones even more so
This is really going to be the second leg of adoption and will catapult GLP1s even further IMO. Rybelsus has not really seen a ton of popularity compared to the injections. That said, Orforglipron is Eli Lilly's upcoming oral GLP1 and it looks to have really good results:
Why use something which appears to have very similar results to tirzepatide/mounjaro but hasn’t been used by tens of millions on people without obvious issues like tirzep?
It's completely illegal -- the drug is not for sale, obviously is not FDA approved, and is not manufactured anywhere, the only safe/legal way to get it is a via an ongoing trial:
As one might imagine though, capitalism found a way. A LOT of compounding pharmacies are now very good at manufacturing GLP1s (not necessarily the case that the knowledge transfers, but I imagine networks/knowledge sharing groups do), so gray market has sprung up to supply adventurous people with Retatrutide.
I don't know about how hard it is to manufacture GLP-1 agonists specifically, but there's an existing enormous grey/black market for peptides for bodybuilding.
It started in the 90s with synthetic GH and since then the number of research peptides has exploded, all of which are readily available on the grey market.
So all the infrastructure for producing and distributing peptides was already there before GLP-1s were a thing, which probably explains why it didn't take long
Why is it illegal? Are drugs illegal by default or has it been specifically controlled/scheduled?
I looked up which drugs are scheduled in the UK and found the list is about 100x longer than I thought it was and in fact the government don't even publish a definitive and exhaustive list of all substances.
At least in the UK, drugs are legal by default in the sense that a specific chemical has to be classified under the misuse of drugs act to be a "drug".
However, specific classes of drugs (synthetic cannabinoids and substituted phenylethylamines etc.) are banned in their entirety by designer drug legislation. This is to stop people producing stuff like mephedrone etc., because there's an almost endless potential for minor chemical substitutions while still retaining the effects.
AFAIK peptides are not covered by any of that legislation, so they are a grey area, hence why they get sold as "research chemicals" "not for human use" etc. Separately it's probably illegal to produce patented drugs like semaglutide through non-official channels, but that would be a civil/commercial matter, not a drugs offence per se
Well for one they're flying in the face of the patent protection in place for Retatrutide -- that said the legalities around distributing prescription drugs or unknown chemical substances is murky (hence "gray" market).
Just to be very explicit here, my profit incentive is selling newsletter subscriptions not selling drugs, if that was the worry.
The thing is that we just won't get any high quality data from the official trials for a very long time, but it looks like it's going to be even better than Tirzepatide which is the current king.
Outside of being simply well-researched, the best thing about GLP1s is that they are safe enough to be taken by millions of people (and they are) -- so anecdata is valuable. It's valuable to know what the "first adopters" are doing and what they're finding and what trends show up there.
[EDIT] Maybe I'm reading the comment wrong -- to answer with good intent assumed, I think GLP1s are basically the answer to obesity on any reasonable time frame.
GLP1s not the answer we wanted (most people would have preferred better food ingredient regulation, more people choosing healhtier lifestyles, etc), but it's the solution we're getting, it seems like.
Right now the only thing I think most can do to help this wave along (unless you're a drug manufacturer, insurer, or politician) is to share as much information as possible on positive and negative side effects, how the drugs work, why they work, etc.
[EDIT2] - Clearly there was no positive intent. I guess it's my own fault I took the time to seriously respond.
The original comment (now edited) was a question about me seeming like a disinterested third party and asking why I am discussing a gray market drug.
Slowing in this context means going down. Basically they look at 'age acceleration', I.e. how old are you epigentically compared to chronologically. They saw a reduction of several years in this measure over a much shorter period, basically meaning their epigenetic ages went down.
Although one of the clocks they used, DunedinPACE, only looks at pace of ageing, so in that case you can only infer that it slowed (as you do not get an 'epigenetic age' figure from DunedinPACE).
I was wondering a similar thing - even as simple as wear-and-tear on your joints, hips and back is less as a smaller bodyweight. I notice I even look younger at a lower bodyweight (up to a point)
We also like to keep track of all the bad ones too[0] (tl;dr they're actually pretty reasonable).
It's amazing what lowering inflation, reducing body weight can do to the body. It's almost becoming irrelevant that GLP1 Receptor Agonists were originally for type 2 diabetes (i.e. reducing HbA1c) -- the effects are profound. Kidney health, heart health, overall health, longer lives -- all for the low low cost of gastrointestinal problems (which can be serious, especially if dehydrated).
Presumably it is in the narrow context of the study, since they need something they can consistently measure and compare
> The researchers used epigenetic clocks to assess biological aging - sophisticated tools that identify patterns of DNA methylation, chemical tags that affect gene activity and shift predictably with age
I think you're very correct to identify the gulf between what the average MedPath headline reader understands "biological age" to mean, and the very specific chemical tags being measured and reported
Any study which uses epigenetic clocks can be discarded. There is to my knowledge no test which produces reliably measurements which don't have big error bars. The only conclusion this study can really make is: Ozempic changes the 'thing' which the epigenetic clock test also measured.
it does seem that there is no reliable connection with "epigenetic clocks" where people are shown to be dying at the same bio age, regardless of calender age......all of the mortality estimating calculations rely on many "factors", so the "ozempic" effects will be just part of a puzzle, where I will bet anything that attitude, demenour, , basic personal conduct will weigh in as the hinge pins that everything else pivots around..........stress, and how that is delt with, and anyone who thinks that one compound is going to reset the whole clock on a complex organism is kidding themselves, which if done right, works ;)
so....it's all for the good
Generic Semaglutide is already produced on a massive scale throughout the world. However, it is unlawful to import and sell and will remain so until 2032 in the USA.
In other markets, where it is under patent, it is significantly cheaper than the $500/month or more in the US currently. For example in the UK it is roughly $150/month USD privately (i.e. not through the NHS).
In China it will be out of patent within two years.
There's a whole little online subculture of people in the US importing the precursors and making it themselves at home for dirt-cheap.
I gather it's extremely easy and basically fool-proof, as far as producing the desired drug and not producing some other, undesired drug. Much easier than, say, home-brewing beer. The risk is all in contamination, which presents a vector for infection.
[EDIT] I don't mean to downplay the risks or suggest people go do this, only to highlight that there's enough demand for this that we're well into "life, uh, finds a way" territory, and also just how lucky (assuming these hold up as no-brainers to take for a large proportion of the population) we are that these things are so incredibly cheap and simple to make, if you take the patents out of the picture.
Not just the current generation of drugs, but they also import and use the next generation that is still in clinical trials and won't be on the market for at least a year. I had it reccomended to me online in a very casual as if it were a supplement. The risk with the is not just contamination but also if you get side effects there's no recourse to sue because you bought it from a chemical factory in China. The new generation of glp peptides is similar to the old one, but still can have unintended side effects as they do work on three receptors rather than the two that the current generation does
Iirc, that pricing will change in the US as Trump will require that the price of drugs to Medicaid patients must match or be less than that of any other developed nation.
Since about 1/4 of the people in the US are on medicaid, close to 90 million, that means the drug manufacturers will probably raise the price for everyone else in the US because they got to get their profits somehow...
In a recent podcast[0], Ben Bikman explained some of background and pitfalls of GLP-1 drugs. When the drugs were first prescribed, dosages were much smaller than the dosages now prescribed for weight loss. Microdosing might be a better and safer strategy.
The podcast is only 3 hours long! The GLP-1 discussion starts at 2:09:53.
It's not GLP-1's in particular, it's protective effects of manifold evolutionary adaptations to semi-regular caloric deficits. Cancer and CHD go way, way up with Westernized diets.
Be very cautious with these miracle drug headlines. There's a strong financial incentive to highlight only the good news.
My mother, a healthy and active 87-year-old, started taking Ozempic because she was overweight and her doctor was impressed by the drug’s supposed miracles. She ended up suffering from severe intestinal motility issues, went through a lot of pain, and had to be admitted to the ICU.
The long-term systemic effects of these drugs are still largely unknown.
> Haven’t these types of drugs been in use for ~15 years?
The predecessor of semaglutide, liraglutide has been sold since 1998. GLP-1 has been studied since the 70s. The first human was injected with GLP-1 agonists in 1993 IIRC.
I know why people hate Ozempic. It is because it devaluates struggle and voids moral superiority of those who did keep themselves from becoming obese by self-restriction before: now these people feel like fools because all of a sudden, everyone is becoming slim, and the advantage of being slim disappears. They naturally question how is it fair. Well, life's not fair.
That's if people think obesity is just the individual's fault. In nutrition there's a distinction between psychology factors, the environment (called the obesogenic environment), genetics, social factors, etc. If you live in the US it must be really hard to avoid being overloaded by food, so I think the real angry group of people will be companies, not being able to force people to eat more, I welcome that!
I hate ozempic because I have no reason to be prescribed it and if it has these anti aging effects or improves self control with other vices, I'm missing out and the ex-fatties will all live longer than me
Sadly it seems to have very little effect in these domains on non-overweight people. In studies, on large groups, Ozempic helps people quit drinking a lot better than it helps quitting smoking - because alcoholics tend to be overweight but smokers tend to be skinny. The higher was someone's BMI, the more pronounced are ALL of the semaglutide effects, even those not apparently associated with weight at all.
"given the replication crisis and outright fraud endemic in scientific publications these days, I have little faith that this research will bear fruit for the general population"
It really puzzles me how people would just pop a pill instead of make some lifestyle changes. Maybe it's just my personality type, but it disturbs me how most people just want something quick and easy instead of doing the actual work and becoming overall better via a real learning journey by struggling through changing bad habits.
But whatever, they do whatever works for them! I don't like pharma.
I guess maybe I'm one of the few who consider "reversing 3.1 biological years" to be a personal insult. Something that polled well in a group of pre-kindergarteners. What happened, some statistical bloodwork metric was tortured to produce such a claim? A mouse population survived the lab a little longer?
Yes, epigenetic clocks discovered in 2010 and even the researcher who discovered them might feel insulted by the phrase of a prescription drug declaring "reverse biological aging 3.1 years"
If you're really interested in that and not just trolling, these are the measures used by the study:
After adjustment for sex, BMI, hsCRP, and sCD163, semaglutide significantly decreased epigenetic aging: PCGrimAge (-3.1 years, P = 0.007), GrimAge V1 (-1.4 years, P = 0.02), GrimAge V2 (-2.3 years, P = 0.009), PhenoAge (-4.9 years, P = 0.004), and DunedinPACE (-0.09 units, ≈9 % slower pace, P = 0.01). Semaglutide also lowered the multi-omic OMICmAge clock (-2.2 years, P = 0.009) and the transposable element-focused RetroAge clock (-2.2 years, P = 0.030).
I find it fascinating how much a pretty large group of people just hate semaglutides and seemingly need to believe that it's some kind of Faustian bargain. I'm not talking about the people who are cautious or suspicious, that's more than reasonable, but it's clear that it's not cautious optimism in many.
"No free lunch" is a reasonable question to ask when evaluating medication, if it would improve the evolutionary fitness of the majority of people. I think this is behind some of the skepticism. If Ozempic is so great then how come our bodies don't just produce more GLP-1? How come we aren't like chimps, with eternally shredded bodies and cheese grater abs, provided we get the protein to support them?
I would guess that getting fat in times of plenty was a feature and not a bug in the ancestral environment, and that's why we get fat today, which is obvious if you think about it. Still, it means GLP-1 agonists are smacking into quick "is it bullshit?" heuristics for a lot of people.
The second point I haven't seen discussed is that weight loss drugs prior to GLP-1 agonists include cigarettes, which (worst case) give you cancer; stimulants, which cause your heart to fail; parasitic intestinal worms, which can kill you but more importantly are just plain gross; and mitochondrial uncouplers, which set you on fire at a cellular level. That's a long history of miracle weight loss drugs which turn out to have horrible side effects. It's not reasonable to think GLP-1 is bad just because of other drugs with different mechanisms, but it certainly causes some skepticism anyway.
> The second point I haven't seen discussed is that weight loss drugs prior to GLP-1 agonists include cigarettes, which (worst case) give you cancer; [...]
Nicotine works just fine as an appetite suppressant without the carcinogenic tar you get from burning tobacco leaves. Similar for other stimulants or stimulant-like substances.
But I agree that they get a bad reputation, despite actually working pretty well, and with manageable side-effects: not worse than what I've heard about the nausea people get on GLP-1 drugs, and much better than the health effects of obesity.
> If Ozempic is so great then how come our bodies don't just produce more GLP-1?
We don't know. But one early signal is that you lose a lot of muscle mass and not just fat, which is not a good evolutionary adaptation if you are an endurance hunter.
https://healthcare.utah.edu/newsroom/news/2025/08/new-study-...
> How come we aren't like chimps, with eternally shredded bodies and cheese grater abs, provided we get the protein to support them?
There are several reasons: Chimps have a higher density of testosterone receptors with a higher sensitivity than humans. Compared to humans, they are essentially roided out all the time.
Humans are also hairless endurance hunters so we naturally have much larger fat reserves (15-25% of body weight vs <10% for chimps) in order to retain body heat and have enough energy to hunt prey till they collapse from exhaustion.
We also live on average more than twice as long as the average chimpanzee.
And average human isn’t spending as much time exercising as chimp does.
And when we did our average lifespan was much shorter.
Time to burn that Gym membership :-p
> If Ozempic is so great then how come our bodies don't just produce more GLP-1?
To store calories so you don't starve. This is a failure mode of evolution and there is in fact "free lunch" when we use technology to reoptimise our bodies to calorie abundance
The other side of this is related to morals. People learned self-discipline by having to moderate their diet. Replacing that challenge with an injection is another example of a world in which people are not challenged to grow as people, but merely go out and buy something to make themselves feel or look better.
There is another way to look at it.
People who don't experience difficulties moderating their diet and could flounder their "self discipline" are now on a level field with people who did have difficulties with their diet. So they feel threatened by it.
Another example of a world in which people are not challenged to grow as people; instead of being happy that more people can get healthy they dismiss the medical advances as "moral failures" since they can no longer feel superior.
Honestly, this is essentially BS. I'd say that 95% of healthy weight people stay that weight because their metabolism and appetite works properly. People who stay in shape by paying careful attention to their diet are a tiny minority.
> If Ozempic is so great then how come our bodies don't just produce more GLP-1
This strays too far into appeal to nature teritory. Evolution made us fit to reproduce not to age.
As for "no free lunch" - we do have a lot of that in medicine historically speaking: iodine salt, clean water, vitamins (C, D), iron supplements, hormone theraphy, vaccines. The field of medicine is no stranger to free lunch.
I am pretty sure uncouplers will make a come back. Just something a little more targeted and safer than good ol’ DNP
none of the things you cited are “miracle weight loss drugs.” they are things people did to lose weight. these are the first class of drugs that actually cause people to lose weight.
I would have to check my sources but I'm pretty sure some of them have been prescribed for weight loss at various times.
DNP and stimulants I'm more confident of, nicotine and tape worms I'm a bit iffy about.
Amphetamine is actually a very effective weight loss drug. And it's sort of orthogonal to the fact that it's a stimulant. Stimulants in general can cause an acute reduction in appetite and temporary weight loss. This tends to stabilise with tolerance, however. As someone with obesity and ADHD, thus was my experience with methylphenidate treatment. And I used to think the weight loss effects of amphetamine were analogous until recently.
Amphetamine and methyphenidate(MPH) have very different ways of acting as stimulants. MPH is an inhibitor of the dopamine transporter(DAT) and the norepinehrine transporter(NET). These cross-membrane proteins essentially "suck up" the dopamine or norepinehrine after neurotransmission, thus regulating the effect. MPH inhibits this process, increasing the effect. This is called a norepinephrine/dopamine reuptake inhibitor(NDRI). Cocaine also works like this, as well as the antidepressant wellbutrin(bupropion).
Amphetamine on the other hand, is a bit more complicated. It interacts with DAT/NET as well, as a substrate, actually passing through them into the neuron. Inside the neuron, it has a complex series of interactions with TAAR1, VMAT2, and ion concentrations, causing signaling cascades that lead to DAT reversal. Essentially, enzymes are activated that modify DAT in such a way that it pumps dopamine out of the neuron instead of sucking it up. How that happens is very complicated and beyond the scope of this comment, but amphetamine's activity at TAAR1 is an important contributor. As such, amphetamine is a norepinephrine-dopamine releasing agent(NDRA). Methamphetamine, MDMA, and cathinone(from khat) also work like this.
Anyway, recently I was reading about TAAR1 and learned something new, namely that TAAR1, besides being and internal receptor in monoaminergic neurons, is also expressed in the pancreas, the duodenum, the stomach, and intestines and in these tissues, TAAR1 activation will increase release of GLP-1, PYY, and insulin, as well as slow gastric emptying.
So in essence, there may be some pharmacological overlap between ozempic and amphetamine(I'm still looking for data on how significantly amphetamine reaches TAAR1 in these tissues, so unclear what the relevance is. But amohetamine is known to diffuse across cellular membranes, so it's likely there is an effect).
Also interesting, amphetamine was recently approved as a treatment for binge eating disorder. Not only because it causes weight loss, but because it improves functioning in the prefrontal cortex(crucial to its efficacy in ADHD), which is apparently implicated in the neuropsychological aspects of BED as well.
Technically, nicotine can be classified as a stimulant: https://web.archive.org/web/20250712041104/https://psychonau...
The American Tobacco Company marketed cigarettes for women's weight control in the 1920's. Lucky Strikes 'Reach for a Lucky" campaign was a big example of this as well, although they marketed it as an appetite suppressant rather than simply a miracle weight loss cure.
Keeping in theme, Ozempic specifically has already been marketed off label as an appetite suppressant, rather than a pure weight loss drug. That's a more modern construct in its brief history.
I was kind of scared of these when Ozempic starting picking of steam for weight loss. I was worried that this would be having more negative effects. Turns out, generally speaking, if used with you doctor, these things are pretty safe, especially comparatively to some of the negatives of being overweight.
And then I saw some of the stories on HN about how it's changed peoples lives for the better. And then people in my life started taking it and singing its praises. I'm very bullish on GLP-1s now and I've very excited to see all the lives it improves. I'm not saying this thing is 100% miracle with no downsides, but this seems to be a generally large net positive.
It's a bit hard for me to comprehend how big of an impact this can have for someone since I've been very fortunate to never struggle with my weight, but I'm (slightly embarrassingly) tearing up writing this because of how many people I've seen have huge positive effects on their physical and mental health (due to body image).
The skepticism people have towards metabolic dysregulation models of obesity is too much.
We know for a fact the inverse happens: girl starves herself for years to slim down to become a ballerina, eventually decides it's not worth it and tries to stop being so dangerously thin and... can't. She never feels hungry. Every time she eats she can only stomach a few bites before pushing it away. Just eat ice cream? Instant puke. She cannot gain weight no matter what.
Obviously she broke her metabolic system and she obviously did it through diet.
Yes it's possible for some skinny people to gain weight. But that doesn't mean every skinny person simply can decide to be fat just by eating. It's like climbing Mount Everest for some skinny people to put weight on, even if they really desperately want to.
I don't think the situation with obese people is all that different.
This concept would be hard to grasp for me if I did not know personally a person facing such issue. I don't think most people can understand that "just eat more" does not work in such cases, because most people can eat just fine even if not really hungry.
> because most people can eat just fine even if not really hungry.
I literally cannot imagine how this is possible. Don't you feel full? Doesn't your body start refusing to swallow? Doesn't the food turn tasteless and start making you nauseous? 100-200kcal over your BMR, sure, but beyond that?
I didn't buy into the whole metabolic health thing -- I thought a calorie was a calorie. But as a person who couldn't lose weight for years due to insulin resistance, just a single daily dose of metformin enables me to lose weight. I was advised to take either that or a miniscule dose of a GLP-1 agonist.
Is there a drug I can take to gain weight?
You have so much choice:
For the pure fat experience I suggest corticosteroids, lithium or a random antipsychotic. Insulin is also very useful here, but a tad dangerous.
If it has to be muscle mass, then anabolic steroids of course are preferable. But beta adrenergic agonists like clenbuterol also seem to have some effect.
And there are many more.
I don't want you to consider it among the flippant replies here but definitely alcohol will work up to a point, it's somewhat of a contradiction though because severe alcoholics are usually quite malnourished and thin.
Ice cream and cheese
mj
Fun fact: eating a bunch of black pepper cancels that out.
This spiked my interest, so I looked around and found a 2018 paper (DOI: 10.1039/c7fo01715d) which, when fed into an LLM, gave me the following information (edited for brevity and clarity). Please note that I did not verify any of the LLM's claims, so take with a pinch of salt. Or pepper.
Antipsychotics tend to do the trick.
Its called sugar
Caution: It's highly addictive
Weight from muscle? Or from fat?
Gaining weight works by putting more fuel into your body than you use. That's physically the only way, there is no way to synthesize energy. Because of caloric density limits, there is no substitute for putting a certain amount of stuff in your body. A pill can physically not contain enough calories.
There are options around that, but that depends on what's driving your personal energy deficit. What's the job that the weight gain intervention needs to do for you, that whatever you try to eat right now does not? What's motivating your current diet? Are you for example disgusted by swallowing anything at all? Are you more partial to liquids than whole foods? Do you dislike sugar in particular?
It's great because we had no other way to address this problem at a population level. Not any realistic ones, anyway.
Like, I figured we were just never going to solve it, given the two possibilities were "radically re-engineer US culture such that moving to the US doesn't make previously-skinny people fatter" (with other countries heading the same direction as us needing to make similar moves, one supposes) or "find a miracle drug". Neither seemed likely. Turns out, decent odds we've managed the latter! Which was always the more likely of the two, but I still wouldn't have rated it as very likely.
It's not like we tried very hard... our whole system is designed around instant gratification, comfort, consumerism and low cost feel good food.
I helped my dad lose 50 lbs by finally, after 10 years, getting him to give up bread, sugar, potatoes. It took buying him 2 months of a bluetooth glucose monitor. Once he saw what certain foods do, he believed me finally. At 65 years old, healthier than I remember since he was 40 and I was a teen. It doesn't require some weird injection.
There's anecdotes, and there's science.
Individually, there's (previously) been nothing better to suggest than "try harder (and, maybe, smarter)".
Statistically it was almost useless, but it's the best we had. It's not bad advice exactly, it's just extremely unlikely to work for long-term, sustained weight loss.
It also very much appears to be the case that weight gain and loss are heavily influenced by environmental factors. Skinnier countries aren't skinnier because the people there have more willpower, it seems, but because they live in a skinnier country and are surrounded by the culture, laws, physical layouts of the created world, et c., that come with that. It'd be kinda weird if we expected "just try harder" to work very well when that's evidently not the mechanism by which skinny countries are skinny. Alternatively, if it is willpower doing it, we're just adding a step, because then it appears that environment strongly influences willpower, instead, since the same observations hold.
Sure, sometimes it works for individuals. In fact, it often works temporarily, causing a yo-yo effect. It can work for long periods (many years without a slip) but that's rare.
If your solution to the obesity crisis is "people need to try harder" your solution is demonstrably not helpful. Can it work for one person? Yes. Over a population, will it? No, it won't, it's amazingly ineffective, even very expensive high-touch interventions involving multiple experts aimed at weight loss and lifestyle change and such are wildly less effective than "inject GLP-1 agonists" or "move somewhere skinnier".
I think it's mainly the food that makes skinnier countries skinnier.
People in the US eat absolute shit. Even the bread is full with sugar.
Good for capitalism if you can feed that to the people and then give them an injection to be healthy again I guess.
Then what should I do :(
Get a GLP-1 under the supervision of a doctor or other licensed medial provider.
As a chronically obese, non-diabetic individual, here in Greece it is impossible to convince a doctor to prescribe anything close to that :(
> There's anecdotes, and there's science.
> If your solution to the obesity crisis is "people need to try harder" your solution is demonstrably not helpful. Can it work for one person? Yes. Over a population, will it? No
Are you an individual or a population though? Take off the telescopes (and data, and science), and look at the world through your own eyes.
No one needs (or can) to address the obesity crisis in the population. The only crises that can be solved are the ones individuals find in themselves.
And odds are very firmly that you'll fail. That's what the science shows us.
having the understanding of the science and self motivated enough to make lifestyle changes already puts you a couple standard deviations out of the population average, such that I don't really think its helpful as a comparison or something to model after
My dad was never told by a single doctor to cut out all processed carbs/grains, and even potatoes, by a single doctor in his life.
So "try harder" isn't going to work when the doctors don't even know what they're talking about.
I'm losing faith in this forum. People would prefer to give people pharma bs because no processed carbs is too much of an ask. Pathetic.
Run a study of your approach and show good results over a cohort for 2+ years and you'll make an entire sub-field of medical scientists very happy.
[EDIT] It's not that your approach can't work, it's that if (for example) people had as hard a time following the directions for condoms as they do following diet & workout plans, we'd never allow condoms to be sold as contraceptives, they'd not even be close to being OK to promote as useful for that purpose. It wouldn't matter if a few people could follow the directions and it worked 100% of the time for them.
I assure you, not buying bread and pastries for your family is a lot easier than correctly using a condom in the heat of the moment. Which is why most people don't use them and use pull out instead. Because even that is easier and better if done right. (I know when to pullout, I don't know if a condom broke before it's too late).
Anyway, it does work, people just aren't told to do it firmly. Doctors dance around it.
You’re a fool. “Pull out” does not protect against pregnancy or STDs. Pre-ejaculate can have viable sperm in it.
You reduce the odds. It is good for those who want kids but not 20 - which is likely the result with nothing at all.
does nothing about stds though.
The zeitgeist has pushed the idea carbs/grains and sugar are terrible over the last 40 years on and off, so that seems to say more about the medical industrial complex, than anything. That's fair, but if that message has been pushed so consistently, why didn't we see a real decrease in the consumption of those things and the associated weight loss?
Because carbs taste great.
I can confirm.
I find that almost all doctors give useless advice. On multiple occasions I've been advised that there was nothing wrong but they can run a scan "if I insist" and then bam, the exact problem I expected shows up clear as day.
They're morons for the most part.
It’s like any other field, most suck and it requires effort to find the smart ones.
I've been told many doctors don't offer "free" solutions specifically because there's no monetary benefit to them.
Maybe if the anti-carb society offered some payola, the story would be different.
Doctors don’t get paid for writing prescriptions. They don’t get kickbacks for writing prescriptions. A small subset of doctors are paid by pharmaceutical companies to run trials or provide expertise, but you can look that up since it’s publicly available information, and it’s not based on them prescribing you anything.
At most a drug rep comes by and brings donuts or something to talk about their new drugs.
Source wife is a doctor.
My dad got box seats to a hockey game when I was a wee lad so theyll sometimes throw money at docs
The rules changed around a decade ago to limit the amount of gifts a doctor could receive from pharmaceutical companies.
Thanks to Obama and the Sunshine Act, this basically never happens anymore.
https://www.mdlinx.com/article/a-physician-s-guide-to-accept...
Increased reporting requirements and a cap on the value of these gifts that is far too low for box seats.
My wife's a physician, and I've seen these things change dramatically. Sometimes some food for the whole office will get dropped off. Or donuts. No one's getting box seats to a pro sports game anymore.
They get paid in lower risk deductibles. If a patient demands a drug they saw on commercials, the doctor can reduce liability by prescribing it in many cases.
Huh? Drug reps have scorecards for the doctors they call on and throw perks at the top performers or influencers. It also depends on the speciality - dermatologists working for price equity mills are almost evaluated like salespeople. Source: girlfriend is a rep.
He could have lost all that weight and still had bread, sugar, and potatoes but instead he gave up what he clearly enjoyed. Now he gets to live out the rest of his life fighting cravings, telling himself he's not allowed to enjoy food. How utterly sad.
Who are you to know what's going on inside his head? What an arrogant comment
Believe me, cutting out bread and sugar completely is 10x easier than some kind of lifelong moderation for a person that has struggled for it already for most of his life.
And he is extremely happy with his new sugar and bread free life of increased mobility, less pain, and much lower blood pressure. At 64, he's learning how to ride a dirtbike and doing pretty well at it.
The choice is no longer between "cutting out bread and sugar completely" and "some kind of lifelong moderation for a person that has struggled." The choice is now between "cutting out bread and sugar completely" and "removing the struggle to moderate bread and sugar."
You're clearly an advocate for your father making healthy choices. So why would you advocate against the use of a drug that makes that easier?
Why waste money and risk side effects for a drug that's not actually needed? Changing your habits is much easier.
If changing habits were much easier, then people wouldn't be using the drug to make it easier change their habits. They would just do it.
> They would just do it.
Telling your mind to do a thing is only ever easy in retrospect and when you find a "trick" that works for you. For some people that trick is getting clear feedback about glucose levels in your bloodstream. But any trick that works for one person might not work for the next. So it is good that there are many approaches.
Changing habits is easy. Still people decide against it because they enjoy those habits more than the result of changing them.
Unless we talk about eating disorders.
Obviously it’s not much easier or the drug wouldn’t be so valuable.
People make such a moral crusade of this - the drug works, people will take it. Behavior modification works in theory and fails for most in practice. Even for those that can make it work usually don’t hold out indefinitely.
I made no moral statement. Behavior modification has worked great for several formerly obese people that I know. They made permanent lifestyle changes without relying on drugs. I really don't care whether people take weight loss drugs or not but the reality is that there are cheaper and safer alternatives.
This is such an absurd statement.
If changing your habits was much easier then we wouldn't need these medications and the world wouldn't keep getting fatter. People have known how to not be fat for a long time, yet the obesity rate has been rising worldwide, even in countries that have traditionally been skinny.
It's not like fat people on the whole are ignorant of how to become not-fat and never attempt to do so.
Because people are choosing deliberately to get pleasure to eat unhealthy stuff instead of being healthy. And that’s a reasonable thing to do. Immediate pleasure trumps future hypothetical gains.
And it’s exactly the same situation with financial education, debt, university degrees, or in general any long term endeavors that requires the sacrifice of the immediate pleasure.
Of course, we still have a non trivial percentage of people that suffer from eating disorders, and use food as a way to emotionally regulate themselves because that’s what they learned as children (child is unhappy, give him a candy…).
> Now he gets to live out the rest of his life fighting cravings, telling himself he's not allowed to enjoy food. How utterly sad.
I don't understand what drives people to write such intentionally asinine comments. Do you get off on hurting others or something?
There were quite a few foods I let go of when I decided to drop weight. Can't say I miss them much, certainly not to the extent to say something like "wow, i can't enjoy food anymore" or "now i'm fighting cravings all the time!!". And I legitimately have no interest in reintegrating them into my diet.
Turns out, some kinds of food are just dumb to consume, and my enjoyment of them is legitimately secondary. To the extent that discovering how harmful they were, they became inherently less enjoyable, and it was well possible for the habits and the cravings to subside over time. You don't try to go hit a balance with crack addiction, why would you try to hit a balance consuming 5 bazillion calorie rubbish?
Cutting out certain classes of foods from one's diet is absolutely possible and there's nothing necessarily wrong with it.
I don't understand. What's sad about giving up junk carbs?
Bread, sugar and potatoes exist on a spectrum from highly processed/refined (truly problematic) to minimally processed whole food versions (nutritionally valuable). There's no reason to give up minimally processed whole food versions of these.
What a bizarre, illogical comment. Did you even read what @throwawaylaptop wrote above? While most of us can handle she carbs just fine, some people have to pretty much eliminate them (regardless of processing level) in order to lose fat.
There is no spectrum for me. I can't eat bread or sugar.
I helped my dad lose 50 lbs by finally, after 10 years, getting him to give up bread, sugar, potatoes. It took buying him 2 months of Ozempic. Once he saw what stopping the cravings for certain foods can do, he believed me finally. At 65 years old, healthier than I remember since he was 40 and I was a teen. It doesn't require some weird bionic arm implant.
I would love to do the same for my dad but i have no idea how to get these stuff.
Lol, a glucose monitor is a bionic arm implant (for $200 total), and an injection disrupting your entire hormone system is what then?
A ridiculous claim.
> some weird injection
What’s weird about it? Is insulin some weird injection? What about epinephrine?
Yes, if you don't need it because there is a natural method that starts fixing your problem in the first week (like cutting all carbs does for being fat), then injecting insulin for your easily fixable problem would also be up there with injecting weird stuff into yourself.
> if you don't need it
It seems like a lot of people need something other than "don't eat bread" though.
Just scale that solution to millions of people and the comparison will be relevant.
If you told millions of people that bread, sugar, pasta and bread are basically killing them, and to flat out stop eating them.. you probably would help people lose weight (and save many lives too).
My dad has finally understood that grains are for people that need help maintain weight or gaining weight.
No fat person should ever be eating them.
But millions of people are being told; "cutting carbs helps with losing weight" is, I dare to argue, commonly known.
> No fat person should ever be eating them.
This is absolutism and controlling. Carbs have their place in a balanced diet, but key emphasis on diet. Too much (like the US diet) isn't good, none at all isn't good either. Everything in moderation. I don't understand why dieting / weight loss conversations are always going into extremes and absolutes.
If I told you billions of people eat bread, sugar and pasta and it wasn't "basically killing them" (whatever that means)...
It's strange to make the culprit of a modern epidemic foods that have been with us for millenia.
Ever look at the ingreadiants for bread? I sometimes bake my own sourdough bread, just flour and water (salt if I remember it).
Billions of people were not overweight when they ate those things. They did not eat them 3+ times a day.
I said in my other posts.. if someone needs help maintaining or gaining weight, eat those things.
If you are overweight, you should be eating ZERO of them.
"Basically killing them" means whatever the current obesity and type 2 diabetes epidemic means.
You don’t think people ate carbs 3 times a day in the past? The majority of humans for the majority of recorded history have eaten some kind of bread, rice, potatoes, porridge, or corn with the majority of their meals.
Also in the majority of recorded history being fat was a sign of wealth. I don't think the majority of humans had a surplus of carbs available to overeat them. It's not that carby foods are inherently bad, there's just something bad about the way they fit into modern society, for some people.
Hey, question, what's the most popular food across Asia?
Modern wheat is a very modern invention. You have to be pretty gullible to believe that something that has only existed for 50 years has existed for millennia.
It took you 10 years to get him to give up bread, sugar, potatoes? This approach would be hard to scale.
I think its great you helped your dad lose weight but what is your issue with others choosing a different path? The health benefits of losing weight are massive . Why is it important to you that they do it how you want them to do it? Study after study has sung the praises of GLP-1s.
It appears that your major issue is that you are simply angry people are taking a short cut. Which seems odd, why would it bother you how someone lost weight, why not just be happy for them?
I got on GLP1s in January. I went from 6'1 240lb to 209lbs with defined abs benching 405lbs at 46 years old. I've worked out my entire life but never been lean like this. I like eating bread (steak, eggs, toast, ketchup and hot sauce is perhaps the single greatest breakfast in the history of the world. The toast is very important!) and potatoes are freaking incredible (mashed with Worcestershire sauce... bruv).
The bulk of my calories are protein but I generally eat what I want if I desire it. I just desire less of it. I had a roast beef sub from Jersey Mike's today with my kid, it was delicious. Their honey mustard is the bee's knees. I had a medium sub though and not a large.
The only change is now I essentially don't eat after 6pm. I just set that goal and the GLP-1 helped me keep it. The only side effects I have had is lower cholesterol and lower BP and that is while running 700mg of test. I'm going to hop on metformin next month after this cycle and target eliminating the fatty liver markers I have had for the last 20 years.
They work friend, they are good for you and they make people live happier healthier lives.
Embrace better living through chemistry.
No but its a lot easier for people who've had trouble and gets results, which is all that matters.
Heroine would also help them lose weight also. Maybe cocaine too, but I'm not sure. So it's not "all that matters".
What matters is, are the negative side effects and long term consequences better for you than the alternatives. One of them is "remaining fat". The other is "doing what other people have proven works.. cut all carbs".
You are showing your own ass with this ridiculous analogy. What are the negative effects of ozempic? Because the negative effects of heroin (not "heroine") and cocaine are well known and grossly outweigh "not being fat."
Is ozempic worse than being fat?
From people I know that have used Ozempic/Wegovy, the side effects are basically that they get a bit nauseated a few hours after an injection. That's it.
> Like, I figured we were just never going to solve it, given the two possibilities were "radically re-engineer US culture such that moving to the US doesn't make previously-skinny people fatter" (with other countries heading the same direction as us needing to make similar moves, one supposes)
Moving to higher elevations in the US causes people to become less fat, so you can do this by moving to Colorado.
https://journals.plos.org/plosone/article?id=10.1371/journal...
It does solve itself due to natural selection based on fertility rate effect of being obesity prone. Life finds a way.
And not just weight loss, but the people I know on GLP-1's have also significantly cut back on alcohol. I think there are ongoing trials around GLP-1's and general addiction.
I've heard similar for gambling, and as one of the sister comments said, things like video games. I'm so curious to understand _why_ that effect is there, but I've heard this so many times now that I do believe that it exists in some capacity. Such an interesting world we're opening up here.
My hypothesis is addiction is generally a secondary application of overeating. Getting pleasure from eating a surplus when you’re not hungry is adaptive (or at least was for most of human history).
In a lot of ways these other behaviors are similar, it wouldn’t shock me if it’s a shared underlying mechanism originally to encourage eating a calorie surplus.
Every person I know who tried to give up smoking has the same story - they were successful for a while and then they encountered some stressful moment (exam, work deadline, etc) and they fell off the wagon. One explanation could simply be that normally we have food stresses which manifests in general stress which we relieve via video games or whatever else. If these drugs turn down the volume of hunger then maybe this has the benefit of reducing the need for stress relieving behaviours in general.
I’ve taken a GLP for two years. It resets your dopamine reward system. It helped me lose 80 lbs and I’m running now. Zero craving for alcohol and sugar. But, my libido is like 3x lol.
If some rando internet dude thinks I’m weak or stupid, fine with me. It’s a drug that has improved my life in ways that are difficult to describe.
As a rando internet dude, that just sounds like you found medication that works for you. That's great!
I wouldn't speculate on the cause of action, however all those activities are linked by activation of the dopaminergic reward circuit, so semaglutides might have some broad based anti-addiction properties by moderating dopamine activity.
It helped me cut back on my drinking significantly. I'm not an every day drinker but a weekend binge drinker and the amount I drink when I drink is down by I'd estimate by around half or more.
I find my compulsion towards videogames is decreased. Not eliminated, but I feel much less compelled to be playing all the time.
I'm curious if this affects smartphone usage. E.g., "compulsive" feed-checking and doom scrolling.
I wonder how it compares to Adderall.
I have an Adderall prescription, although I rarely use it. Adderall lets me focus on things longer, with distractions staying in the background. If anything, Adderall makes me too focused on a task.
If I were doom scrolling when Adderall kicked in, the risk is I'd continue doing it for hours.
Adderall produces a very, very different experience and is prescribed to address a very, very different root cause.
However, amphetamines such as Adderall were also sometimes prescribed for weight loss. I'm surprised it was done so rarely before Ozempic was a thing. They were quite effective.
The side effects of adderall are pretty bad. If I'm on a dose that's high enough to suppress my appetite, then I get a very bad crash in the evening. I start to feel like if I want to enjoy life after work, I need to take another adderall to feel normal. That disrupts sleep, and then things start to get really bad.
Stimulants have well documented downsides. It’s one of the hard aspects for adults with adhd as you often need to taper as you develop heart issues.
That may be a correlation without causation. Don't know if you lost much weight, but if you did, a huge benefit of losing weight is to increase the level of tonus, and suddenly activities that require no tonus (playing video games, watching TV) become less compelling relatively to other activities.
Definitely lowered alcohol consumption for me.
I no longer get that dopamine rush of the first drink.
Some people go as far as describing it as anhedonia. I kinda get it.
Not for me, in fact my diet involed not taking any dessert, which GLP1 made fairly easy, so I ended up allowing myself to drink a couple of glasses of wine in the evening, which I never did before. I never noticed an alteration of the sense of taste, just a general feeling of satiety (particularly on an empty stomach).
Though many people mention feeling sick as a common side effects, I can very well imagine that they would lose any pleasure from food and drink.
Friend of mine took it for his wedding and completely stopped gambling after having a problem with it. He says he's never been more focused in his life on being productive with work and family.
I've heard this as well, but (anecdotally) they haven't reduced my interest in alcohol at all.
Would you consider yourself addicted? Perhaps it stops the addiction without stopping the general desire to drink with friends.
The cynic in my thinks this will its undoing. Some huge fraction of alcohol profits come from a small portion of drinkers. If these G* peptides help these poor people their drinking under control, it would take a huge wrecking ball to the profits, and thus to the taxes. Can't have that.
They're very expensive drugs so it would be one lobby against another. However given that they're so expensive, I would think that broke, uneducated alcoholics just won't have access to them, so those profits are safe...
I think you over estimate the liqour lobby and underestimate how much of alcohol profits likely come from luxury purchases
Reduced healthcare, policing, and other costs that are paid for with tax dollars from lower alcohol consumption would almost certainly be a net gain over the piddly tax revenue from alcohol consumption sales.
So you're saying it's also going to harm the revenues of the health care industrial complex and the police state? That's not going to help its case.
There's still plenty to learn about long-term effects, but it's hard to ignore the sheer volume of real-world stories from people saying it gave them their lives back
The same thing with keto. People will swear it's unhealthy but like, the alternative (outside of Ozempic and co) is being overweight...
We think obesity is basically going to be gone in <7 years. GLP1s don't work for everyone, and the side effects can be severe, but this these drugs are basically safe, and incredibly effective.
This is going to accelerate when every one and their mother (with industrial capacity) starts making generic Ozempic/Wegovy (Semaglutide) next year due to Canada's patent protection lapse[0].
https://glp1.guide/content/novo-nordisk-patent-protections-l...
> We think obesity is basically going to be gone in <7 years.
I wonder if this is for wealthy people
(...who might be the target market - being overweight might be a disease of affluence)
Nope! It won't be, because capitalism.
In 2026, patent protections that lapse are going to cause a tidal wave:
https://glp1.guide/content/novo-nordisk-patent-protections-l...
For context, the previous calculus was:
https://glp1.guide/content/patent-expirations-for-glp1-recep...
(~2033 for the US)
Theoretically, the tidal wave of generic Semaglutide wouldn't hit the US or EU due to patent protections there... But see the aforementioned note about capitalism.
Note that there is already generic Liraglutide as well:
https://glp1.guide/content/another-generic-liraglutide-launc...
Tirzepatide (Mounjaro/Zepbound) > Semaglutide (Ozempic/Wegovy/Rybelsus) > Liraglutide
But having any of these available is a step change.
> (...who might be the target market - being overweight might be a disease of affluence)
This might be true on the margin but is mostly untrue these days. The lack of access to healthy unprocessed food and the free time to exercise are becoming increasingly problems for those who are NOT wealthy.
I think that, just like with stomach reduction surgery, people are going to find a way to overeat and gain weight while taking Ozempic too.
Nope, because the change is actually in the brain.
https://glp1.guide/content/research-on-glp1-signaling-in-the...
https://glp1.guide/content/research-suggesting-glp1-is-a-bra...
https://glp1.guide/content/are-glp1s-primarily-brain-drugs/
This is the killer feature of Semaglutide and GLP1 Receptor Agonists widely. They were originally commonly thought about as digestion-slowing, and while that is part of it, the real change is that it's a brain drug.
Oh also, on whether people gain back the weight:
https://glp1.guide/content/do-people-regain-all-the-weight-l...
tl;dr - most people (i.e. over 50%) do not.
Uh, so, first, I'll say that bariatric surgery is largely a successful (if extremely invasive) intervention. It is not the case that people who do that surgery somehow compensate eat back to the same level -- on average, they don't. And second, the GLP-1s just massively reduce the urge to snack/eat. I'm sure they are less effective for some people than others, but on the whole they are miraculously effective for the population that overate habitually (the obese).
Many people (will only speak to America), view being fat as a literal moral failing. Gluttony or overeating are not the sin, but being fat.
(From that perspective:)a miracle cure that allows someone to stop being fat is like an indulgence (in the Roman Catholic sense). It’s a cheat, a shortcut that allows the unworthy to reach a state they do not deserve.
My opinion is to wait long enough to validate there are no long term harms, but beyond that, yeah, adjust the priors, it could be a modern aspirin.
> Many people (will only speak to America), view being fat as a literal moral failing. Gluttony or overeating are not the sin, but being fat.
I feel like I've seen and heard more of the opposite: The trend is to avoiding anything that might make someone feel blame for arriving in their situation.
With obesity the trend is to blame some combination of "our food supply", trending science topics like microplastics or the microbiome, and genetics.
I've heard countless people explain to me that dieting doesn't work for them. It's not hard to find people claiming they ate <1000 calories per day and still gained weight. Even Eliezer Yudkowsky, a figurehead of the "rationalist" movement, has written about "metabolic disprivilege" and claimed that his genetics do not allow him to lose weight through dieting. This thinking runs deep.
What's interesting about GLP-1 inhibitors is that they modulate the intake portion of the diet, which shatters these previous notions that some people had "metabolic disprivilege" and simply could not lose weight by reducing caloric intake. They just make it easier to reduce food intake.
> I feel like I've seen and heard more of the opposite: The trend is to avoiding anything that might make someone feel blame for arriving in their situation.
> I've heard countless people explain to me that dieting doesn't work for them.
I think you're being a tad reductive – "dieting right now doesn't work for me for reasons I can't control" and "reducing calorie intake will help me reduce weight" aren't necessary contradictory, and don't imply "I'm going to attribute it all to biology/blame it on something general".
Anyway, let me assert the opposite: as a partner of a nutritionist who's talked (with anonymity) about her clients, the majority of the people she's worked with, who struggle with sustainably reducing calorie intake over the course of years, come to dieting with that logic, and _then_ struggle against specific barriers, and _then_ blame themselves. (A recent example: "because of my work schedule I don't get enough sleep, which leads to weight gain and time only for frozen food – on top of my predispositions".)
In that case, GLP-1 inhibitors as an intervention _complements_ the way her clients think about dieting.
> and _then_ blame themselves.
I was responding to a comment about Americans blaming others, not dieters blaming themselves.
The concept of "blame" isn't really helpful anyway. The problem I frequently see is that blame becomes something to be avoided, which turns into a game of externalizing the source of the problem, which makes people think the problem is out of their hands.
A similar pattern happens in addiction and addiction counseling, where well-meaning friends and family try to soften the blow by telling the person that the addiction was not their fault, it was the result of their circumstances or bad influences. Addiction counselors have to undo this thinking and find a way to gently get the person to take some ownership of their role in arriving at the problem, which is the first step to having some control over correcting it.
For nutrition, when people convince themselves that they have a hidden metabolic disadvantage that makes caloric restriction not work for them, they're more likely to give up than anything.
> Even Eliezer Yudkowsky, a figurehead of the "rationalist" movement, has written about "metabolic disprivilege" and claimed that his genetics do not allow him to lose weight through dieting. This thinking runs deep.
I thought EY's point was different. Am I misremembering? I thought it was about not being able to do mental work productively when dieting enough to loose weight(maybe maintain a low weight too, though I do not remember that being mentioned explicitly).
It's a long story. His description of "dieting" was extreme calorie restriction. He was eating something like 800 calories per day (don't quote me on the exact number) and then was complaining that he didn't feel well when doing that (to the surprise of absolutely nobody).
Then it turned into a false dichotomy between the 800 calorie severe calorie restriction or no dieting at all. Then he just started declaring he'd delete any comments that suggested dieting.
It's clearly both. Someone with stronger motivation to stay healthy can survive in adverse conditions, but a society that pushes unhealthy lifestyle harder is going to catch more people out. It's obvious that Americans aren't just all individually lazier than the rest of the world. Their cities and food are unhealthy.
Genetics do factor. It's not just a question of genetics affecting metabolism. People literally don't feel hunger with the same intensity as one another. It's like sex drive. There are both very horny people and asexuals out there. There are also people who routinely forget to eat. For many people though, the notion of "forgetting to eat" seems completely alien, because those signals are much stronger for them.
I agree with you, but it's important to remember that "dieting down" is way harder for a lot of people. I am and always was skinny through my life. Whenever I need to eat less, I can do it without much effort. However, I have friends who would faint if they tried to diet down the way that I do. I don't know why that happens, but I've seen happening and it changed my perspective about this subject. If Ozempic can help with that, I will never criticize someone who uses it.
And also the idea that it is "easy" to lose weight is completely out of touch. If it was there wouldn't be millions of people trying hard, spending money on trying and failing for decades, and entire businesses addressing that.
RFK Jr's "let them eat less" is paradoxically the modern version of "let them eat cake"!
> And also the idea that it is "easy" to lose weight is completely out of touch. If it was there wouldn't be millions of people trying hard, spending money on trying and failing for decades, and entire businesses addressing that.
This is a touchy topic, but I would like to point out that you're missing the obvious confirmation bias that comes with this observation.
There are many people who modulate their weight by changing what they eat, how much they eat, reducing snacking, meal planning, and changing their shopping habits.
You don't see them among the millions of people failing to lose weight or paying for expensive solutions because they quietly solve their problem.
I'm also not suggesting it's easy, but we should acknowledge that many people do successfully control and modulate their weight through dietary and habit changes. There's a survivorship bias problem that occurs when you only look at the remaining sub-group who has the most difficulty with this.
> I'm also not suggesting it's easy, but we should acknowledge that many people do successfully control and modulate their weight through dietary and habit changes.
For example: weightlifters. It’s standard operating procedure to “bulk up” - periods where lifters overeat to promote muscle growth - and then diet to “cut” weight to drop the fat gained during the bulking period while keeping the muscle. They tend to be extremely motivated individuals though.
With 40% of US adults overweight, that is a substantial plurality though. It's not confirmation bias when it's more then 1 in every 3 people.
> It's not confirmation bias when it's more then 1 in every 3 people
If you construct your argument to exclude the 2 out of 3 people who are not overweight and then point out that the remaining 1/3 is overweight, that's the definition of confirmation bias.
It's also a disingenuous argument because not all of those 40% are actively trying and failing to modulate their weight in any way. Most people just don't care.
No way that it’s only 40%. Well over half are overweight. Any definition claiming only 40% is lumping in a lot of fatties with the “not overweight”.
They got the right number with the wrong descriptor. It's about 40% obese (and 78% overweight, last I remember).
and there are people who don't get fat no matter what they eat. Not sure what difference it makes to the millions of people I am refering to. Not even sure what is your point.
> and there are people who don't get fat no matter what they eat.
This is a myth.
When you actually track what these people eat, their daily caloric intake averages out to numbers you'd expect. At best, the difference between "fast metabolism" and "slow metabolism" people in studies comes out to a couple hundred calories per day.
You may witness someone consume 2 pizzas and a soda in one sitting without getting fat, but that person is consuming fewer calories for the rest of the day or the week to offset it.
I think what they mean is "they eat whatever they want and however much they want" and still don't get fat.
Some people just only want to eat an amount that doesn't get them fat. They aren't using any willpower or anything, they just don't want to eat more than a healthy amount for them.
I am not one of those people (I am overweight when I eat as much as I want), but I am for other things. For example, I don't drink very often (only maybe 10 times a year) and don't get very drunk when I do. I just don't feel a desire to drink very often. It takes zero self discipline to not drink for an extended period of time because I don't have the desire for it.
On the other hand, many alcoholics struggle mightily to avoid drinking. It takes all their willpower to not drink.
Everyone is different in their ability to avoid different addictions.
I think many people confuse simple with easy.
It IS simple to reduce your weight. There are like, two things you need to do. It is, however, VERY hard to actually do those things.
But it's not.
What you're referring to, is the basic concept of thermodynamic calorie in/calorie out. Yes, you can "just" reduce food and lose weight if you hit deficit numbers.
But if you don't do it correctly, you'll feel like trash, you'll suffer bad cravings, and put yourself in a stressful mental situation for days, possibly putting your job at risk.
You have to:
- Eat less than what you're already eating
- But enough to nourish yourself so you keep being in good shape for your work and hobbies
- Manage hunger
- Make the change sustainable so you can keep doing it for the rest of your life.
It's specially hard when your work is entirely sedentary, you live alone and, ironically, when you have a salary that let's you order food every day.
A lot of people don't have it hard. Maybe because they have someone cooking for them at home, because they meal prep the entire week, or because their work is so physically intensive they can just wing it and burn everything with what they need to do for a living anyway.
Inaccurate in my opinion. Let's say you eat 2500 calories a day usually. But you want to lose weight so you reduce it to 1800.
Except your calories are from pop tarts.
If you ate 100 calories of pop tarts every hour you're awake for total of 1800 calories... At the end of the month you'd be fatter.
If you ate 1800 calories of pop tarts once a day in 1 hour, you might maintain weight or loose a little. Maybe.
If you had 3600 calories of pop tarts in a few hour window, and then didn't eat again for 48 hours, you'd lose weight in a month.
Insulin control is 99% of losing weight. Yes thermodynamic blah blah, but unless you pay attention to hormone control that controls metabolism in general, it's not going to work without insane willpower to keep your 'calories out' higher than your body wants.
If you repeated the 3600 calories every 48 hours with beef instead, you'd lose weight like never before.
Insulin control is about managing hunger more than a direct cause for weight.
You don't even need to do keto or wacky "just meat" diets to handle insulin. Protein consumption prevents insulin spikes for around 1-2 hours after eating. Also, proteins and fats slow down digestion.
Turns out, the good old Mediterranean diet is spot-on for a healthy lifestyle.
? Insulin is not about management of hunger. I think you got your hormones mixed up.
But yes, meat and vegetables is basically what I'd recommend. Never pasta or bread or sugar unless you need help gaining weight.
He’s probably thinking of ghrelin (or NPY), but leptin and insulin both act as satiety signals too, although weaker than the hunger signal.
Meat and vegetables would make me sedentary from having inadequate glycogen for physical work and exercise.
How about: some pasta and bread to enable physical exertion.
> If you ate 100 calories of pop tarts every hour you're awake for total of 1800 calories... At the end of the month you'd be fatter.
This is thermodynamically impossible unless your daily calorie use is less then 1800 calories.
It is only thermodynamically impossible if you assume 100% efficiency in energy extraction from food, but in practice we only extract a very small amount of energy from matter. Thermodynamically you could extract ~10^12 kcal from a Pop Tart if you converted its mass into energy.
Not that I agree that for a human metabolism meal timing makes much of a difference in energy extraction, but it wouldn't be thermodynamically impossible.
It's insane to me that people keep talking about the energy in part. Forget that.
Realize that WHAT you put in can change what energy out is.
If I gave you 1800 calories of vodka at 8am, would your use the same amount of energy during the day, and even make it to your 7pm gym? No.
Ok, well sugar isnt exactly the same obviously, but it can also affect what you do that day, how your body acts, your brain even.
Your energy out gets totally messed with after you have tons of alcohol for obvious reasons. Something similar happens on sugar/spiked insulin levels. Can you willpower through it and increase your energy out by running til you drop dead and lose weight? Sure. But it's not easy.
What's way easier is not having the insulin spike in the first place.
Yes it can affect what you do. That's the calories out part of the equation.
Nobody claims that the quality of what you eat has no effect on you, but every study shows that if you maintain the same calorie intake and expenditure it doesn't really matter how you consume the calories or how you expend it.
Well then luckily that shows you hopefully how bad studies are. Because I assume that you agree that eating 100 calories of Pop-Tarts per hour for 18 hours for 30 days, would give you a different result than eating 3 days worth of Pop-Tarts in a few hours once every 3 days for a month.
To not understand that would mean that while believing some studies, you completely ignore all the studies that have been done on insulin and weight gain.
> Because I assume that you agree that eating 100 calories of Pop-Tarts per hour for 18 hours for 30 days, would give you a different result than eating 3 days worth of Pop-Tarts in a few hours once every 3 days for a month.
I agree that you would feel very differently in those situations and it's likely you wouldn't spend the same amount of energy unless you really make an effort to do it.
I don't agree that if you do make an effort to spend the same amount of energy you would have different results with regards to weight loss.
Two weird assumptions here...1, that massive amounts of constant blood sugar/insulin don't affect metabolism.
2, that in the face of crazy long term insulin/hormone disruption, people will continue to be just as active as if they had a sane diet of mostly meat and vegetables.
I'm starting to see why everyone is so unhealthy.
Are you saying raising your insulin levels hourly, 18 times a day, will not do anything to your metabolism? Did you even read my post, or did you just instantly reply with the same pedantic reply which my post was specifically meant to address?
> Are you saying raising your insulin levels hourly, 18 times a day, will not do anything to your metabolism?
What metabolic effect do you expect from raising your insulin levels hourly?
The first law of thermodynamics applies to closed systems, which your body is not. Yes it is true that, very broadly speaking, eating more results in weight gain past a certain point. But first principles are not the most proximate reason for that by a long shot.
That's exactly why I liked being on keto. Never felt hungry, had way more energy, mental health improved a lot. No other diet had those effects. I've been off it for a while and I feel gross again.
Right, so exactly like I said, it's very simple. If you want to lose weight, reduce calories.
If you add extra modifiers like "I want to feel great while doing it" and "I want to lose weight while sedentary" and "I want to continue eating whatever stupid thing I want" and "I need to be able to scroll tiktok for at least 3 hours, leaving no time for cooking", it gets much more complicated.
Side note: LOL at "but if you're craving food you might get fired!!1!" - this is professional victimhood at its finest.
Even then, limiting calorie intake isn't all that difficult; there's a reason why intermittent fasting took off and so many people were getting results from it.
Not necessarily. Some people respond well too intermittent fasting but not everyone. Some people respond to keto but not everyone. And just because you respond doesn't mean it's gonna take you to where you need to be.
I've always been skinny but for some reason I've gained weight recently. Even with keto, intermittent fasting, tirzeptide, and workouts twice a week I have only lost 5 lbs in months. When I was skinny and forgot to eat, I would feel a little crappy but still could function. Now I begin to feel incredibly depressed, I can't sleep nor focus. This solidified it to me that there's a circuit in your brain that controls feeding and if it's out of whack it'll punish you until you eat. Dieting takes months and no one can go that long without sleep. So it's still a practical problem, its just hard to see if your system is well calibrated.
> Even with keto, intermittent fasting, tirzeptide, and workouts twice a week I have only lost 5 lbs in months.
If you're combining a ketogenic diet AND intermittent fasting AND a GLP-1 inhibitor AND exercise and you're still losing less weight than observed in the Ozempic studies, it's likely that there's more to this story.
Ketogenic dieting does not automatically translate to weight loss. Keto simply makes it easier to reduce caloric intake. It's actually very easy to gain weight on a keto diet due to the high caloric density of consuming that much fat.
> Now I begin to feel incredibly depressed, I can't sleep nor focus.
Honestly if you're having these dramatic negative effects from minor caloric restriction with GLP-1 inhibitors, something else is going on.
Limiting calorie intake is easy. Consuming near unlimited calories is even easier and a lot more fun.
I will tell you the secret: resistant fiber supplements.
There's other zero-calorie foods too, but they tend to cause intestinal discomfort rather than improve it.
Ive heard this same sentence, verbatim, repeated throughout the course of decades for particular fad diets. Decades.
The irony is that all that
"it's so easy"
"it's just calories in, calories out"
"if you eat according to this plan and make sure to get 8 hours of sleep a day, you won't even feel the cravings"
Is stuff that fat people say. They totally buy into it and buy all of the products to help them convince themselves this is true. Then they get disillusioned when it doesn't work, have a crisis of faith, then go to the next fad to get over the self-hatred caused by their failure at sticking to something so easy.
Intermittent fasting is great. It got me from 225 to 165, kept it off for the past few years with no effort (my entire metabolism recalibrated to 165-175, I guess.) I also know people who cry actual tears when they're very late for a meal, or panic. Those people need therapy and/or maybe an injection to artificially lower their appetites to the level where I also artificially lowered my own appetite.
Intermittent fasting is no more natural than injections. Dieting is modernity.
I’m certain IF more closely resembles how humans ate for millions of years, not knowing when our next meal would come before becoming an agrarian society, and we haven’t had much time to evolve since then.
So, yeah, dieting is modern, but so is an abundance of food. Both are equally unnatural.
It is that difficult, otherwise everyone would do it.
> Many people (will only speak to America), view being fat as a literal moral failing. Gluttony or overeating are not the sin, but being fat.
As an American with a sister with thyroid issues, I can say that is absolutely not true for the majority of Americans. People are mostly sympathetic to those who are not obvious slobs.
> People are mostly sympathetic to those who are not obvious slobs.
Maybe once they hear the story, but most people assume every fat person they see is a slob
How would you even know the cause of obesity of a stranger? This is why viewing being fat as a moral failing is mistake regardless of the cause. I'm pretty sure a lot of people view your sister the same way just because they have no idea she has thyroid issues
People are mostly sympathetic when it's physical issues. Psychological issues are treated as diseases of the soul that you only need God or willpower or whatever to fix. And most fat people are fat because of the incentives in our society, but admitting that also goes against certain political ideologies...
What are the incentives for people to be fat, out of curiosity? Do you mean farm subsidies for corn, for example?
It's not that there are incentives for you to be fat, but there are incentives for things which happen to cause you to be fat.
The car industry is a huge one. Making people drive everywhere means more car sales, more fuel sales, more infrastructure built for more cars. And it also makes you fat as a side effect.
At a low level, yes, corn, but at a high level: more consumption = more money.
Everyone benefits from you being fat. Your doctors, your car manufacturer, food manufacturers, everyone. Except maybe health insurance. But they're not hurt too too much.
There is no doctor on Earth who goes to work and thinks "thank god for fat people or I wouldn't have a business".
There's plenty of doctors and surgeons who wish there were less fat people, because they enormously complicate doing surgery on and managing in hospitals.
> There is no doctor on Earth who goes to work and thinks "thank god for fat people or I wouldn't have a business".
I agree, but this isn't how incentives work.
Ultimately, there are billions of dollars at play here that rely directly on obesity. The mechanisms of the market and human behavior transcend moral judgement.
> There is no doctor on Earth who goes to work and thinks "thank god for fat people or I wouldn't have a business".
What about everybody that works in liposuction?
With respect, neither of you are qualified to speak for majority of Americans, but given the amount of effort, money, ink, and television dedicated to looking better and losing weight combined with the fact that there's even a thing called fat phobic that even requires definition just to push back on all that...
I think there's sufficient reason to believe that "Overweight = bad" is a common standard that at least people hold themselves to.
We must live on different timelines. Pre ozempic America was the proudest nation of fat people I have ever encountered (excluding the costal elites of course).
It's weird because I agree with you, but also have to acknowledge that the "pushback against fat phobia" was for some reason a thing.
Third American here, and the push for fat acceptance was so little of my media consumption that it surprised me so many people spent so much time and energy on the topic.
I agree with this take but want to add that once everyone is doing it, these opinions will change drastically and everyone will pretend like they were never against it.
Another interesting question is where do people go from there? What is the next signal of virtue, I wonder.
You can be gluttonous and still thin. I eat 2 lbs of ground beef a day, with tons of cheese on it. For breakfast I have 6-8 eggs, with cheese. I have my morning coffee with heavy whipping cream. For desert, I whip up some of the heaving whipping cream and have it with frozen berries thawed out. It drives gfs nuts but they're too anti fat to try it.
That still pales in comparison to what a lot of obese people are consuming. Some ground beef is nothing compared to chugging a 2L coke a day.
Eggs have about 60 calories each.
Cooking 2lbs of ground beef could yield a little over 1500 calories (Source https://www.uhhospitals.org/health-information/health-and-we... )
A tablespoon of heavy whipping cream is 50 calories.
There's nothing incompatible with what you wrote and a 2500 calorie diet.
This confuses a lot of people who associate certain foods with becoming fat, or think that eating fat makes you fat.
It's entirely possible to eat what you described and maintain a neutral weight.
There isn’t any real secret to this: This combination of foods leads to you eating a calorically neutral amount every day.
That’s a horrifying amount of saturated fat per day, though. This is an extreme risk for heart disease.
That’s a horrifying amount of saturated fat per day, though. This is an extreme risk for heart disease.
I keep hearing this, yet after 13 years of keto my cholesterol is still 100. Being fat is much higher-risk than eating fat.
I'm all for obese people taking Ozempic if they really need it, as well as thoroughly studying its long-term benefits and risks, but the fact that we're at the point of considering medical intervention as the population-wide solution to obesity is an abject failure of policy. Looking at our nutritional guidelines, you'd think everyone in America was an extreme athlete. All we have to do is:
1. Take something like the food pyramid, and put vegetables on the bottom, put fat/dairy/coconut and protein/meat/eggs/soy/mycelium in the next level up, put fruit in the next level up, and put starches and sugars on top. In other words: eat real food, mostly plants, without extreme high-carb macros, and treat fruits as dessert. Reverse the failed policy of demonizing saturated fat, and make this the official dietary recommendations for at least a generation.
2. Provide an incentive structure to use lower-GI ingredients in food products. For example, largely replace sugar with inulin fiber sweetened with stevia and/or monk fruit, and largely replace flour with alternatives made from blends of flax, wheat gluten, and resistant starch; no one will notice the difference. Stop letting Cheerios of all things market itself as "heart healthy", at least with its current formulation.
In this world, people would eat way more veggies because they'd grow up with parents and restaurants preparing them properly (with saturated fat and salt). Even for those who didn't, high fiber fortification of UPFs would provide a reasonable backstop. The low-fat/low-salt era's reframing of healthy food as "bland" is a crime against humanity.
For any fat people we still have after that, sure, put them all on Ozempic. It just shouldn't be the expected default that unmedicated people are fat while the medical establishment shrugs its shoulders and doubles down on half a century of empirically bad advice.
I agree of course. Only note is when I say coffee with heavy cream, I mean like half a cup of it into espresso to make a cream latte.
And over a cup whipped for desert.
But I'm also 6'4".
When I ate the standard American diet I was about 40 lbs heavier than I am now.
I'm not a Catholic, but wasn't the idea of an indulgence that God intentionally allowed an alternative path to redemption, such that if you buy an indulgence, you are (at least by their definition) worthy and deserving?
I always thought of this as essentially the same idea as with Civ allowing you different paths to victory.
My point was that many people view ozempic and other drugs like Martin Luther viewed buying an indulgence: a cheat for the undeserving.
I thought Martin Luther's issue was more with the organization selling indulgences than the undeserving buying them. He preached justification by faith alone. Not some org selling justification.
Yes indulgences mean something different in Catholicism, they remit the "temporal effects" of Sin ie its spiritual consequences but don't "forgive" it like "Sacrament of Reconciliation" would..
I think that parent is perhaps confusing it with the sin of Gluttony.
The weight loss mechanism largely just comes from suppressing appetite though, so it still lines up with the penance for sin narrative. It’s not that different from wearing a hair-shirt and whipping yourself if you find yourself having lustful thoughts. Only instead of a whip you just feel kind of uncomfortable and nauseous if you eat too much.
I'd describe the effects as basically the opposite of self-torture. Self-torture is dieting/fasting without the drugs. With them, it's great. No afternoon light-headedness and difficulty concentrating, no hunger pangs, no "hangry" effect, no cravings you have to keep suppressing. Just smooth sailing. (though experiences do seem to vary—as do dosage levels)
That's true of semaglutide, but newer peptides like tirzepatide (a dual-agonist) and retatrutide (a triple agonist) have additional effects like improving insulin sensitivity, and simultaneously slowing the release of glucagon and activating glucagon receptors, which directly increases fat oxidation and thermogenesis.
>My opinion is to wait long enough to validate there are no long term harms, but beyond that, yeah, adjust the priors, it could be a modern aspirin.
it can be more than aspirin. Such an effect on glucose should, among other things, be affecting cancer, probably in a very positive way.
>My opinion is to wait long enough to validate there are no long term harms,
What's your threshold on that? How many years is "long enough"? Trying to calibrate my own sense of risk.
I'm a late adopter to most things.
my estimate would bigger than others and I would put it at 30-50years.
I take smoking as a cautionary tale, in the beginning it was pushed as not just a recreational thing but a healthy activity that bring benefits with papers published to sing praises about it. my parents were even nudged by their teachers/doctors/etc when they were young to try smoking.
now we all know that smoking is beyond bad and all that early "research" was just people paid off by big companies to promote it.
> I take smoking as a cautionary tale, in the beginning it was pushed as not just a recreational thing but a healthy activity
While i agree the gist of what you are saying, also important to mention that humans started cultivating tobaco when mamoths still roamed the Earth. There was indeed a concentrated pro-smoking publicity campaign by tobaco manufacturers in the 1930s, but it was hardly “in the beginning” of our tobaco use.
I think a lot of people share similar concerns, but the benefits of a successfully therapy are so extreme it would take quite a lot to derail ozempic. People easily gain 5 or more years of lifespan by not being obese, avoid myriad related health conditions, and are truly much better off. It would take a lot to reduce someone's life expectancy by a comparable amount and we haven't seen that much besides gastrointestinal issues.
We performed the surgical options like stomach reduction before this which come with serious danger for comparison
Under-discussed benefit: being able to have all your clothes actually fit at the same time (no wardrobe scattered between your "skinny" weight and your "fat" weight and rarely being in the right place for more than a handful of pieces to fit entirely correctly) so you can spend up a little on nicer clothes without worrying you'll only be able to wear them part of the time. Worst case, you start to pack on a little too much and they start getting tight, you increase the dose or go back on the drugs for a week or three (or just do it the old fashioned way—hey, it works some of the time, temporarily) and ta-da, right back where you want to be—you're not going to pack on weight and find yourself unable to lose, so buying "skinny clothes" isn't mortgaged against your future success at forcing yourself to eat less.
Not OP but 10-15 years for most drugs. Took about a decade for the general consensus around Oxy to change.
Haven't these been out for a very long time, just not for weight loss?
A quick Wikipedia search shows Exenatide was FDA approved in 2005 for diabetes.
Ozempic itself has been in use for almost a decade now (originally approved for type 2 diabetes in 2017). Many millions of people have taken it, without much in the way of serious complication.
Exenatide had been in use since about 2005, and by 2019 had more than a million people on it. Some of those patients have literally been on it for 20 years. It does have a worse side-effect profile than Ozempic (or the more modern GLP-1's like zepbound), but even then the benefits outweigh the risk for those diabetics.
Today it is hard to argue the benefits of modern GLP-1s don't outweigh their risks. They've been extensively tested, the class of drug has been around for decades, and they are used by many millions of people.
I personally lost 120 pounds on Zepbound in a little less than a year. It's been life changing, and anyone who thinks I might be less healthy now is very clearly wrong. Literally every aspect of my life has been greatly improved.
There’s two sides to that coin. Obesity has known long term harms. So what we are looking for in a deal breaker can’t be a small but statistically significant increase in some cancer or other. We’d need something as bad as smoking to outweigh the benefits.
> Gluttony or overeating are not the sin, but being fat.
This is a strange thing to say. If you do something normal, and you end up in a normal state, why would that be a moral failing? There's no such thing as "overeating". Different people eat different amounts. The same person eats different amounts at different times.
> (From that perspective:)a miracle cure that allows someone to stop being fat is like an indulgence (in the Roman Catholic sense). It’s a cheat, a shortcut that allows the unworthy to reach a state they do not deserve.
This is incoherent. If you believe that being fat is a sin, but that the things you do that make you fat are not sins, then a miracle cure that makes you thin removes the only sin you were committing. You can't be unworthy if you're not fat. In order for a miracle cure to be "cheating", it is necessary that the sin is in the behavior and not the result.
Everyone defines normal differently and people are quite good at judging those that are not their normal.
Did you mean to respond to someone else?
> I find it fascinating how much a pretty large group of people just hate semaglutides and seemingly need to believe that it's some kind of Faustian bargain.
There have been some scandals about "miracle drugs" which bad effects have been found only years after being on the market. And side effects can be crazy: I use D2 agonists which works wonder to handle a prolactinoma (like shrinking a tumor with a simple pill every 2 weeks wonder), side effects of this kind of medication can be different addictions (sex, gambling, purchasing etc.) which is always fun when you're one in a thousands to get it.
You've got a crowd of people raised in a Calvinist society who think nothing good comes without suffering, you've got people who feel this is a cheat where discipline should win out, and you have a bunch of people who are used to all easy solutions coming with either a bad lottery ticket or externalities on other people/the environment.
They can all agree that they're waiting for the other shoe to drop.
That said, we are at a point where people are overweight enough that getting exercise has its own risks, and taking a medication that allows you to be more active is likely to cancel out some of those downsides. As long as you do both I have no problem with people taking ozempic, mounjaro, etc.
I would prefer if we figured out what other than cultural changes is making everyone have symptoms of inflammatory dysfunctions. There is more than one thing going on. Processed foods, contamination, some microbe that doesn't culture in agar. And it's spreading to more of the world.
> Calvinist society who think nothing good comes without suffering
Or, some of us older folks have been around long enough to understand that we are, in an uncontroversial and factual way, the long term medical trial, and long term effects found in that trial, along with the eventual market withdrawal, may not show up until 10 to 20 years later, creating a healthy distrust in the money/corporations behind the, sometimes outright crafted [1], early medical trials.
[1] https://www.nature.com/articles/d41586-023-02299-w
How many times has a drug had negative effects that only showed up after 10-20 years? Out of all the drugs that have been widely prescribed in, say, the last 100 years? And it’s not even actually a new drug class - Liraglutide was approved in 2010! Should we wait until the clinical trial participants all die of old age until we put a drug on the market?
Most the nonpharmaceuticals I could list from memory, I had to google the medication
Nonpharmaceuticals
- microplastics
- bisphenol A
- asbestos
- nicotine
- DDT
- fungicides like HCB
- PFAS
Pharmaceutical
- benzodiazepines
- Terfenadine
- Benfluorex
Of the 528 new drugs approved over the period of interest, a total of 22 (4.2%) were eventually withdrawn. Between 3.9% and 4.4% of the drugs approved in each 5-year period were eventually withdrawn (χ2 = 0.04, p = 0.99 for difference among 5-year periods). The median time between approval and withdrawal was 1271 days (interquartile range 706–2876).[0]
By some estimates 7% of US have used semaglutides. That is 24.5M people. That could be 24.5M people who have benefitted but if it turns out that there are long term consequences, that's a lot of people who are now all in that ship together when at least some of those users could have chosen lifestyle intervention rather than chemical intervention. If we take the 4.2% recall rate that gives an EV of 980k people in the US who will suffer adverse effects from semaglutides
[0] https://pmc.ncbi.nlm.nih.gov/articles/PMC4085091/?utm_source...
I wasn’t talking about non-pharmaceuticals, and neither were you. Non-pharmaceuticals don’t go through clinical trials, and they mostly don’t require any pre-approval. So that’s clearly just trying to pad your list.
Benzodiazepines do not have effects that only suddenly show up after 10-20 years of use. The serious side effects/withdrawal show up with a few months of heavy use, sometimes sooner. They’re also actively prescribed (with some appropriate caution), so a really weird one to lead with.
There are actually quite a few drugs still widely prescribed today that cause similar QT prolongation to terfenadine (e.g. quetiapine). The difference is they are for more serious conditions where the other options have similarly serious side effects, and terfenadine has to compete with Benadryl. No reason to have to get periodic EKGs just to keep your sinuses decongested in allergy season.
> Of the 528 new drugs approved over the period of interest, a total of 22 (4.2%) were eventually withdrawn. Between 3.9% and 4.4% of the drugs approved in each 5-year period were eventually withdrawn (χ2 = 0.04, p = 0.99 for difference among 5-year periods). The median time between approval and withdrawal was 1271 days (interquartile range 706–2876).[0]
I’ll give you the benefit of the doubt, and assume that you just didn’t care to read the paper once you assumed it agreed with you and did not selectively quote on purpose. From the same paper:
> Of the 22 drugs withdrawn, 11 first had a serious safety warning and 11 did not (Table 2). The median time between the Notice of Compliance and withdrawal was 1271 days (interquartile range 706–2876).
So, the percentage you quoted was double what we were actually talking about here. On top of that, I don’t think you finished reading what you did quote; the median time to withdrawal was < 5 years, and if you actually look at the table only two drugs with serious safety issues actually hit the 10-20 year range you mentioned.
> those users could have chosen lifestyle intervention
We’ve been trying all kinds of “lifestyle interventions” for a long time, from doctors telling people to exercise to semi-organized campaigns of body shaming. It hasn’t worked for the vast majority of people in practice. So unless you have some actually novel idea here, you’re essentially trying to get people to switch from a drug that works to the power of positive thinking. Good luck with that.
It took us 10-20 years to find out about tardive dyskinesia due to antipsychotic medications and the long term dependency and withdrawal effects of benzodiazepines. Two entire classes of drugs that are now in common use, so it’s not unheard of.
I’m not saying we should take Ozempic off the market but don’t be fooled into thinking that we’re immune to unintended consequences just because we did a few studies (almost all of which were on diabetics with controlled diets).
At no point did I say we were immune to unintended consequences. Just that demanding every drug be used for 30+ years before you’ll touch it is not actually making an analysis of the tradeoffs involved.
Also, the drug classes you listed are not great examples. Benzodiazepines don’t fit what we’re talking about at all: it’s common to develop tolerance and get serious withdrawal symptoms from a few months of heavy use. You definitely don’t need to take them for 10-20 years (or even the 8 years since Ozempic was approved) to notice the serious side effects. If Ozempic killed you if you quit it cold turkey, we would already know. Psychiatrists were not unaware of what happened when you took too much Valium back in the 60s when it was first introduced. It’s just that they (and society in general) had an attitude toward risks that is totally alien to modern sensibilities (and to be clear, I think it was bad).
First-generation antipsychotic’s incidence of TD was strongly correlated with dose, which was strongly correlated with having schizophrenia and other mental illnesses involving psychosis specifically (as opposed to other indications like bipolar without psychotic features or major depression). Getting TD later in life but being able to live outside of an asylum (they were still around when first-generation antipsychotics were commonly prescribed) is probably a tradeoff many of these people would have taken, even if they knew about it.
That first paragraph could be the preamble to every conflict in my life and it would be evergreen
> I would prefer if we figured out what other than cultural changes is making everyone have symptoms of inflammatory dysfunctions.
I personally hope it's just cultural and sugar/hfcs. Because some alternatives might be grim to reckon with just from a humanistic/grief perspective: https://pubmed.ncbi.nlm.nih.gov/34484127/
You've also got the crowd who would argue that there's nothing wrong with being fat in the first place and that are scared of society pressing on this matter again after years of pushback.
As someone who was 100 pounds overweight for a long time, and now isn't, that mindset is really dangerous and preventing a lot of people from living life to its fullest.
There is never any reason to be cruel or unkind to people who are overweight, but pretending that it doesn't have negative consequences or is even "healthy for me" or whatever is really harmful.
I think there is a large chance that this crowd referenced arguing for "this" is even smaller than than the population of (25? 50?) trans ncaaa athletes that all the rubes believed was ruining america. Loudmouths on the internet exist and suck but don't represent everyone.
This comment summarizes a lot of things I struggled to vocalize, thank you.
> That said, we are at a point where people are overweight enough that getting exercise has its own risks, and taking a medication that allows you to be more active is likely to cancel out some of those downsides.
And yet we rarely ask or say "maybe I should just eat fewer calories?" Unless you have some other disorder that prevents normal bodily function, that does work (and would be viable I'd imagine for the majority of people being prescribed).
But it requires patience and discipline which are basically non-existent for the majority of the population.
You think that is rarely asked?
I studied chemistry at university and my master's was in medicinal chemistry.
My main takeaway was that "chemicals = bad" is a better heuristic for a starting point where you then look for exceptions or accept them as the last resort after exhausting other options.
Would you let AI loose on the software of your airplanes or nuclear power plants? Medicine is like a sensible idea that should be ok but is hard to rein in and localise to just the area of effect, we hope that it only makes the change we ask from it but we ultimately can't really say with certainty that it isn't also doing something else
I'm actually generally more surprised that people are so trusting of taking medicines and pop pills like they're candy
I think you've got to the nub of it. I worry about e.g. gall stones risk in 10y. But, friends worry it shows a lack of moral fibre or something. They aren't the same kind of worry. One is paranoia about past drug emerging issues and the other is tied up in belief eg poor addicts own their own fate, fat people should htf and eat less, depression isn't real... it's usually a short path to "I don't want to have socialised medicine for poor and old people"
The drug companies are very good at making new drugs with high profit potential look better than they are. I'm worried semaglutides are another fen-phen, Vioxx, Quaaludes, Trovafloxacin or OxyContin.
One thing to watch for is effect size: how big of an anti-aging effect does Ozempic confer relative to other good interventions? Were the subjects doing other solid anti-aging interventions like the Fasting Mimicking Diet (FMD)? If not, the 2 interventions might affect the same pathways with the result that if you are doing FMD, you get no additional benefit from Ozempic.
Fen-phen is particularly interesting here because people reported that not only did it help them lose weight, it gave them more willpower and changed their personalities for the better.
Don't worry, GLP1 RAs are nothing like those other drugs. In fact I'd really challenge you to examine even one of the correlations there, the scale of research, use, known side effects, effectiveness is completely different.
The idea that people might only benefit from something like Ozempic a little if they were doing some other intervention before is irrelevant, because no one is doing those other interventions. Requiring people to suffer before providing useful, known-safe and well-researched medication is silly.
Medication is technology.
I think that's a completely reasonable concern to have, it doesn't seem to be the case wrt obesity but for the myriad of other potential effects it's important to keep in mind.
I'm not even ready to concede that it is a good weight-loss drug -- but then I haven't really investigated much, so I'm just repeating what I heard from researcher Ben Bikman and maybe other researchers. I heard that most people choose to discontinue it after 4 or 5 years or less, regain most or all of the weight, then refuse to go back on it.
Tirzepatide (and likely other GLPs) have limitations that are rarely brought up in the general media
- Patients have about 72 weeks to reach maximum loss, they don't lose any more weight after 72 weeks even on the highest dose.
- Patients appear to immediately gain the weight back as soon as they stop taking it.
It's right in the phase 3 trial outcomes paper:
https://pmc.ncbi.nlm.nih.gov/articles/PMC10667099/
I suspect that this info is intentionally down-played so that it doesn't affect sales.
I've been on Zepbound for ~25 weeks now and one of the first things my doctor told me was that this was a lifetime drug. He pointed out that I had a choice, of lifetime drugs. I needed to do something to get my cholesterol under control. That meant start statins now and likely add blood pressure meds and diabetes meds in the next 2-5 years. Alternatively I could start Zepbound, which would likely address all 3 and result in better quality of life in the next year. So far it seems like it is doing exactly that.
I'm sure some people are going into this without that knowledge, but people are being told this is a lifetime commitment. What you don't see a lot of is why people stop taking it. There's some cases of people losing and then stopping, but the majority are because insurance is forcing people off of it. Just look at the recent CVS Caremark forced switch from Zepbound (2nd Gen) to Wegovy (1st Gen) in July.
I'm fairly certain that literally every doctor tells literally every patient this. Mine sure did. It's also on the handout your pharmacy gives you, the website for the drug, and in fine print at the bottom of most commercials.
Nobody expects a single does of ibuprofen to cure your headaches for life. Similarly, this doesn't "fix" your biochemistry for life, you have to take it in order for it to work.
> I suspect that this info is intentionally down-played so that it doesn't affect sales.
Yea, hard to figure out why drug companies keep producing "Faustian bargains" in our current system. What galls me is people assume the best for new drugs instead of forcing the _for profit_ entity to prove it's actually safe and useful.
To the extent that, reliably, the first comment on these posts on Hacker News are some wishy washy anecdotal emotional blackmail garbage that completely obfuscates the point and runs direct interference for these large profitable organizations.
To the extent that it's hard to believe that these posts even on this tiny corner of the internet aren't bought and paid for. We live in a society that cherishes organized crime and denigrates hard work. I would not look forward to "new drugs" in this regime.
Novo Nordisk is majority owned by a charity and is therefore not a for-profit entity.
> What galls me is people assume the best for new drugs instead of forcing the _for profit_ entity to prove it's actually safe and useful.
That's what the FDA approval process is. They already did that in 2017.
Novo Nordisk Foundation is a nonprofit but Novi Nordisk the pharmaceutical company is very much a for profit entity - it’s publicly traded on several stock exchanges including the NYSE. The foundation owns most of the voting shares but only about a quarter of all outstanding shares.
I've had a few friends on it. They definitely lost weight, but the GI issues were too much and when they went off of it they gained it all back.
I've read (anecdotes from people in the fitness/body-building space) that the default dosing could be too high for many people. And the side-effects seem to ramp up with the dose.
IE, if you're getting weight loss at 1/2 the default dose, you might want to stay there, even if your MD wants you to increase to the default.
[default uses loosely here - people build up from a low dose over the span of weeks/months]
And the weight gain is due to a lack of lifestyle change. The drug just numbs your appetite, so you don't eat as much. If you go off the drug and return to over-eating, yep, you gain the weight back.
I also suspect many people lose the weight too fast and go too far. "Ozempic butt" is a joke for a reason - people loose a bunch of fat, but the massive calorie deficit also means they aren't exercising (no energy, and they probably weren't before the drug either), so they've probably crashed their metabolism.
I tried it. I started down about 80 lbs from my heaviest, but a good 40 lbs from ideal/20 lb from healthy weight.
The first time I tried it I followed dosing guidelines for ramp up; side effects were horrible, didn’t lose much weight, and it just kept getting worse.
Second time, after a few months off, I started at lowest dose and stayed there. Side effects were better to start but ramped up again. Eventually my digestion stopped entirely and I couldn’t eat without pain; that actually was good for weight loss but very unhealthy (e.g. despite being hungry and lightheaded the pain kept me from eating more than 400 calories). Eventually it passed but I couldn’t justify taking it after that.
Basic side effects: exercise intolerance (higher starting rate, much faster increase exertion, chest pain after ~150bpm when previously I could run nearly an hour and go up past 180 without issue), fatigue in the morning (despite essentially maintaining my pre-ozempic nutrition), significant increase in resting heart rate, significant decrease in HRV, and digestive upset (basically alternating diarrhea and constipation).
Many of these side effects are well known, others less so.
Ozempic, when micro dosed, did help reduce hunger and make a weight loss diet easier to sustain, until the side effects got so bad I wanted to comfort eat. But mindfulness and healthy lifestyle are similarly effective without crippling side effects.
Try Zepbound. You lose more weight with far fewer side effects.
Although, you may still have issues. It does just sound like there's something unique about your chemistry. I don't think that many of those side effects are even in the ballpark of normal.
I would like to try it, but I don’t think it is available from shady internet doctors and insurance won’t cover it because I’m not diabetic. Shady internet ozempic passes the cost-benefit test (barely, considering I can successfully lose weight without it it’s just hard). Full cost out of pocket it does not. Maybe in a few years.
I would worry that the side effects I care about are not the side effects that others report being improved on zepbound.
Protip: Get an ultrasound on your liver. Almost every obese person has (what used to be called) fatty liver, and that's usually enough to justify the prescription to your insurance company.
Have you looked into Tirzepatide? Basically a combo of ozemspic plus a GIP drug. Again, anecdotes from bro-science, but appears to allow lower dosing and reduced side-effects.
Very much the default is too high and the bro-science was indeed early on this. I’m super sensitive and had the bad negative reactions at 1/10th the starting dose. It’s been a wonder drug for me though, finally able to put my life back together after ME/CFS all but destroyed it.
> when they went off of it they gained it all back.
To make matters worse, even ibuprofen is a scam. I stopped taking it and my headache came right back!
More seriously, if you stick to it the GI issues go away after the first month for most people.
Just about every single adult woman in my wife's extended family is on Ozempic. None of them are obese at all. Or diabetic. They are all using it to "lose a few pounds" (we're talking like less than 20 pounds; Yes, as you might expect, there are some unrealistic beauty/success standards in my wife's family). So I think there are a lot of people who are annoyed by that, because of the message it sends to completely healthy-weight girls/young women who don't look like professional super models in a swimsuit.
Since we have young daughters, that aspect of Ozempic really bothers my wife. Though she would have no issue with obese/diabetic people using it to get healthy.
Personally I do think it is a miracle drug and I'm glad people are getting healthy because of it.
To be fair, if you're an average height american woman (5'4"), the nominally healthy BMI range is just 37 pounds wide from 108 to 145 pounds, so 20 pounds can be pretty significant.
I fall into the same category as your wife's extended family. I used it to get to the weight I feel most comfortable and I've gone back on it periodically (like after 5 weeks of work travel) to get back within 5 lbs of that weight (where I can manage the additional weight loss on my own).
When being fat becomes more of a deliberate choice (due to the drug accessibility) I do wonder how society and society's expectations Will change. Will women be even more pressured to "bounce back" during postpartum? Will the "baby fat" we only get to have during adolescence be eliminated and drop out of the shared experience of growing up?
There's also a lot of concern within the eating disorder community about the potential for abuse, because these drugs are so easy to get a hold of by lying on telehealth (could be argued that I've abused them by getting them when they're not truly necessary).
How does one get Ozempic without being overweight?
There’s armies of grey market don’t ask don’t tell e doctors who will give it to you with no request for evidence of being overweight.
Thank god for poor regulation. Unironically thank god and may this situation continue.
So the South Park special was kind of based on reality?
It's a tool, like anti antidepressants. When used right and in the good settings they can be amazing, when used as a magical pill without treating the underlying issues and not understanding its mechanism of action you're in trouble.
I know people who used anti depressants for a few weeks, while going to therapy and fixing their shit, they were out of trouble in less than 6 months. But I also know people who've been basically been taking pills for their entire adult life with absolutely no sign of getting better, the pills just make them cope slightly with their shitty routine/job/&c. while completely destroying their body and making them numb to everything. Same for ozempic, I know people who think you just swallow the pill and that's it, they still have horrendous diets, drink 800cal stabucks "coffee", snacks on sweets all day long, and they're actually gaining weight...
Another good example would be sleeping pills, take them once a year to fix your jetlag and they're amazing. Take them for 10 years because you can't fix your routineof watching tv shows in bed until 1am and "need" pills to fall asleep quickly, you'll just fuck up your circadian rhythm for good and it'll be 10 times harder to get out of the cycle
If you truly want to fix your shit virtually any tool is good, but if you just want a magic pill without putting any work you're doomed, the main issue is that it's advertised and sold as a magic pill
There were even people who felt this way about anesthesia too. To survive in that era, they had to believe that suffering was somehow good for healing (or at least good spiritually) and talked about anesthesia as if it were cheating the natural god-given order.
Are you talking about MMother Teresa? She wasn't that long ago...
I think this might be revisionism. A lot of people feared early anesthesia because it was far more dangerous than today.
I also notice people will make note that 'eccentrics' from the 1940s-1950s hated air conditioning but it helps to understand it was a dangerous technology that regularly injured and killed people back then, especially in its earlier days the adults of that period were children during. AC didn't get safe until fairly recently in the 70s, 80s and 90s. It would catch fire or leak poison that killed people in their sleep. Some people just saw it as an unnecessary risk. Same with early fridges. When they leaked, that leak could be fatal as poison or explosion.
It wasnt until later that these technologies got safer and even now today, we consider full anesthesia a last resort and will always try to get away with local or twilight anesthesia because full anesthesia does regularly injure, disable, and kill people. Evolution didnt design us to be trivially "shut off" like this. Injecting us with substances like that will always come with risk.
In other words, a lot of those people weren't mindless luddites, but people who assessed their personal risk and said "nope, not worth it." I think that's perfectly fine.
I'd argue the revisionism of today and the ego justifications of the time were just that, ego protection. Its far easier to say "Well, I'm tough, I don't need that," then "I'm scared of that." The former is rewarded in our individualist capitalist society. The latter is vulnerability and honestly which is often only punished in a society like ours. We see it today with people with limited access and affordability to healthcare in the USA putting off care or engaging in various home remedies, alt-medicine, supplements, or conspiracy-culture-esque pharma drugs gotten cheaply via the gray market.
I see a similar hesitancy around anti-alcohol addition treatments like naltrexone. People almost _want_ it to be difficult to quit (or lose weight), like there should be some moral struggle associated with it
Its the same root cause: they think alcoholism or alcohol dependency is a moral failing so there should be struggle and punishment to overcome it.
Alcoholism is a moral failing, and the struggle and punishment are real, and come not only from outside, but also from within.
One can try to rationally argue their way out of alcoholism being a moral failing, but then one notices that in a similar way they can “whitewash” any other moral failing, and the words lose their meaning completely.
Yet people use these words to mean something, and abuse of alcohol falls under that meaning, and every society in existence has always cautioned against and condemned it.
I think there's a justifiable fear/dread when things that used to demonstrate virtues no longer do so.
For instance, being in shape used to (usually) demonstrate discipline. Art or music used to demonstrate attention to craft and practice. Knowledge demonstrated time devoted to study.
This isn't to say that the world is worse with these advances (I'd be hopeless without search engines, and I am grateful that people get to live longer and healthier with semaglutide), but I think a little bit of mourning is understandable: what used to be the fruits of hard work are now a dime-a-dozen commodity.
Naturally skinny people hate Ozempic for the same reason I know many talented engineers who hate AI coding.
It is not fun when your superpower becomes a commodity.
I'd wager that you can only call an engineer talented if they know enough to hate AI coding.
They are living rent free in your head, they really don’t care.
I think those engineers don’t like you because you find unrelated subjects to justify your favorite scam.
Thank you for your service
Was waiting to see this comparison. Glad to see that meritocracy is becoming the pejorative it was always meant to be. Meritocrats are unironically bigots.
> I know many talented engineers who hate AI coding.
People whos primary skill is coding, hate AI coding. No talented engineer hates AI coding. The distinction is this: a coder knows how to use their tools, an engineer knows how to work with people, understands product, process, users, and knows how to use their tools.
Talented engineers hate the HYPE around AI. And those of us old enough to remember sigh and think "This is just dreamweaver all over again". It is ESB's with "drag and drop" workflow tools. AI is just another useful tool that a good engineer can pick up and put down where appropriate.
As a talented engineer, I hate AI coding because it doesn't do what it says on the tin. If GLPs made people hallucinate weight loss that wasn't actually happening, I'd be angry about them too.
Ever seen "Shallow Hal"?
I’m in the cautiously optimistic camp. I’ve seen two people puke their guts out the day of their doses, but nausea isn’t so bad compared to the health consequences of being overweight.
Some studies have shown people just drop back to their old habits when they stop, and that long-term use isn't good (pancreas, kidneys, etc). It's life changing for some, but like any medication, it shouldn't be used casually.
It's similar to the hate that some people have for SSRIs when they've never tried one.
I'm not a fan because it's expensive and once you go off of the drug the weight comes back on (at least from what I've read). That's not a trade-off I want to take lightly.
There's also something to be said for gaining the discipline to do it yourself along the way, which may lead to keeping more of the weight off in the long run.
We also don't know what the long term side effects of it will be, if any.
I don't find any of that unreasonable to me. I'm saying this as a type-2 diabetic who could stand to lose a lot of weight.
> I'm not a fan because it's expensive and once you go off of the drug the weight comes back on (at least from what I've read). That's not a trade-off I want to take lightly.
This isn't true
https://glp1.guide/content/do-people-regain-all-the-weight-l...
The rest of the incorrect points other people have basically covered, so won't repeat.
Is teaching the discipline lesson worth the shorter life people would live without this medication? Maybe we could find another way to teach people discipline that doesn't maintain a threat to their health?
> I don't find any of that unreasonable to me. I'm saying this as a type-2 diabetic who could stand to lose a lot of weight.
Gonna be incredibly blunt, but talk to your doctor and get on GLP1s. Take a low dose if you want.
GLP1s are incredibly well researched and effective. Imagine dying of a heart attack early because you refused to properly research effective, low-risk medication that is being used by millions and recommended by professional organizations and doctors widely. Real Steve Jobs energy.
> We also don't know what the long term side effects of it will be, if any.
The first GLP‑1 receptor agonist was commercially released in April 2005, meaning 20+ years. People who often repeat this: If 20-years, and tens of trials, isn't long enough to "know" then where is the line exactly?
Thalidomide by contrast was available for 4-years, Vioxx for 5-years, and Rezulin for 3-years by contrast.
> There's also something to be said for gaining the discipline to do it yourself along the way, which may lead to keeping more of the weight off in the long run.
That doesn't work; we know it doesn't work both from small and large scale studies, and population evidence since 1970s. So you're promoting the same thing we've been doing, and failing at, for beyond all of my lifetime. Feels like a religious belief at this point, rather than following the data and what we know from it (i.e. that objectively does not work, and has never worked).
Is there something new you know that health experts haven't known as Obesity as increase up through 40.3%+ (with overweight being 73.6%+)?
"Discipline" doesn't exist, or rather it's a feature of your brain and not something you can necessarily learn. GLP-1 inhibitors and stimulants (modafinil, amphetamine, etc) are drugs that literally give you "discipline".
Habits are something you can learn though, and having more discipline helps you form them.
> We also don't know what the long term side effects of it will be, if any.
What are the long term side effects of NOT taking it? The article implies it could be early death.
Well, considering that the drug was originally developed not for weight loss but for type 2 diabetes management, it's not terribly radical to be skeptical or outright dismissive of it as some miracle weight loss drug (even if that is a consistent side-effect).
The whole rush to get people on the thing feels like an opportunistic pharma grab (because it is). The outcome of those sorts of things is never in favor of the individual or their well being.
Part of it probably stems from how fast they went mainstream, especially with the weight loss hype
I agree, and I am a consumer of those myself, which did absolute wonders. And of course I will assign vastly more weight to my own experience, than to the opinion of some random guy on the internet who only read about it.
However, we also need to be conscious that this is a very very big business, and given the size of the market, is happy to pour billions into some studies that will demonstrate that it has all the benefits in the world and cures everything. Addressing obesity is a humongous benefit in itself, and helps with all the medical conditions that result from it (which in balance makes most mild side effects irrelevant). I am a lot more skeptical about those dozens of claims that it improves X by Y% (often low single digit). Most medical studies in general are dodgy, show minor benefits on small samples in a massively multivariate environment, which more often than not are statistical noise carefully selected, when the approach don't have outright flaws or fraud.
> I'm not talking about the people who are cautious or suspicious, that's more than reasonable
Yah.. The track record for public health related items that have a really rapid uptake after release is not great.
> find it fascinating how much a pretty large group of people just hate semaglutides and seemingly need to believe that it's some kind of Faustian bargain.
Its just inductive reasoning. Most things are not free, let alone miracles. Nearly everything in life has a cost.
In part that's because historically weight loss drugs have had nasty side effects that only become apparent after years of use.
It’s the same people that hate vaccines, fluoride, and sugar substitutes. They feel like those interventions are too good to be true.
There are people who are going to hate anything like that, because it makes a very difficult task (losing weight) significantly easier. And we hate it when the damned kids, what, with their Tok-Clock and deadass rizz, have it easier than we did back in the day.
That being said, the fact that we let our society in North America get to the point where something like semaglutides are such a huge deal is something to honestly hate, and I think some of the misdirected hate is really a hatred for that.
I think Ozempic is just a symbol of what modern life looks like. Obesity is a problem that 100% could be solved with a cultural shift (see Japan), but instead we decide to use medicine. It's like, humanity at large grew such big brains because there was evolutionary pressure to be intelligent, but now we're using intelligence to remove that pressure. Which would make sense if we redirected that intelligence to something else, but we don't.
I think the reason why we don't see aliens is that intelligent life isn't sustainable long-term, and there's a long list of reasons why intelligence leads to self-destruction.
Sure, a lot of problems could be solved with a cultural shift, but most people are in a rat race to survive
And those in politics are not interested in change since because (the cynical part starts here) they are selected / sponsored by billionaires who own the media, or go to politics as a job and not to help anyone but themselves
On a side note storing fat to feed the brain in case of bad times makes sense. In the past there were no convinience stores, nor refridgerators
> And those in politics are not interested in change since because
It's not about "big media", it's about the fact that average voter is an idiot. This a fundamental flaw of democracy.
I am one of those people to some extent. For me, it's the naturalistic fallacy I can't get over. I drink caffeine daily, but the idea of hijacking my hunger with an injectable induces dread. I would like to believe that there are no long-term side effects, but:
1. We have to trust the data of for-profit pharmaceutical companies and their trials. They are incentivized to produce optimistic results.
2. It's relatively new (insofar that a lot of people are taking it). Opiates were touted in a similar way until the other shoe dropped. There exists an undefined line in time where I would feel more comfortable.
3. It is/was made of a poison from an animal.
4. The extreme benefits are overwhelmingly in obese candidates. Keto is the same way; I tried it and it was not for me because I am not obese.
I'm actually open to any sort of evidence that will change my mind. No name calling please.
>It is/was made of a poison from an animal.
Caffeine is an insecticide.
> I find it fascinating how much a pretty large group of people just hate semaglutides and seemingly need to believe that it's some kind of Faustian bargain.
Some of us also remember previous weight loss drugs which had similar levels of hype and later got pulled because of really bad side effects.
If I needed to lose 100+ pounds, I'd be at my doctor tomorrow asking for it. The side effects of 100+ pounds are way worse than anything semaglutide might cause.
For people who are using it to lose 10-20 pounds, the tradeoff isn't as clear.
I am cautiously optimistic and hope that semaglutide lives up to the hype. lots of people will benefit if it does.
Apologies if this sounds argumentative but I would be super curious of the cross-section of people that are pro-semaglutides and also anti-vaccine. I am fascinated by that too! (And I trust that HN will share a lot of great datapoints)
>seemingly need to believe that it's some kind of Faustian bargain
I mean, that's because that's literally what they need to believe. A majority of people has been brought up on an incredibly moralized account of human behavior, and if it turns out you can just pour some GLP-1 drugs into the drinking water and basically fix a whole bunch of issues it will become obvious that a therapeutic framing is the appropriate way to look at these things.
For people who live in a world of vices and sinners who have to swear off the devil, this throws a pretty big wrench into the whole story, it's much more than just a drug.
I personally believe the theory that obesity in the US is caused by other things in the water supply[0], so adding GLP-1 inhibitors would cancel them out.
[0] obesity appears to be caused by moving downstream/to lower altitudes, and has increased in farm and lab animals at the same rates as humans.
I think it's a similar thing to those who are morally invested in human overpopulation and not consuming resources for climate change reasons and such.
The techno-optimist GLP analogs like solving these things with clean energy and other modern marvels throws a wrench into that story.
every time in recorded human history when there's be a panacea or cure-all it's generally been snake-oil.
There are a lot of side effects, of this type of medicine - many which were not really prevalent when it was prescribed on-label.
> every time in recorded human history when there's be a panacea or cure-all it's generally been snake-oil.
That's just not true at all. Like, not even close.
Almost everything we've invented in medicine has been free. As in, little to no downsides and just makes things better. And not just in medicine - look around you, compare it to 100 years ago. A lot of stuff is safer, for free.
Think about infant mortality. We went from 1/4 100 years ago to 1/1000s. For free. Surely birth must be more painful now, right? No... we got rid of the pain too. Well surely mothers die more, right? No... They die orders of magnitude less too. Well surely the Vitamin K shot must have SOME downside? Pretty much no, it just pevents bleeding out.
does HN not know what the word "panacea" or the phrase "cure-all" mean?
Aseptic technique is a panacea or cure-all IMO.
But usually when someone says panacea they don't actually mean a cure-all. Because, obviously, that's impossible and will always be so. They mean something with lots of uses and no downsides.
Wouldn't the side effects, combined by the accompanying lifestyle changes key to making this medication most effective, show its not a panacea or cure-all? The fact there are these second order effects with such incredible impacts would lead me to believe its more mechanistic than magical with how much obesity effects all sorts of body systems
Antibiotics?
There are lots of miraculous, life-saving drugs that have minimal side effects and aren't snake oil.
Metformin, insulin, many vaccines, some statins, and some antibiotics are clearly on that list.
Statins cause uncontrollable anger in some people… but also lower it in other people.
eg https://journals.plos.org/plosone/article?id=10.1371/journal... finds it reduces anger in men but increases it in women.
> panacea or cure-all
specifically, is what i said.
"GLP-1s are beneficial for many conditions downstream of liver dysfunction and metabolic disease" is a much milder claim than "cure-all".
also in the news in the last couple months was "promising for breast cancer" and another cancer (can't remember, don't care), and depression as well as some other mental health disorder.
If you would like to give me money i would be happy to do the research on what claims have been published about GLP-1 inhibitors since they became prescribed off-label.
I assure you it's more than "many conditions downstream of [...]", unless you want to concede that mental health like depression and dementia are related to gut bacteria, then we can be friends.
also, i caught wind that by December 2025 it's going to be recommended / "proven" to work for erectile dysfunction. At a certain point, we're mincing words.
As someone who saw miraculous cessation of lifelong immune issues on it, saw another friends dramatically improved allergy symptoms, another lifelong smoker finally quit, and other friends generally get in great shape, I actually do believe it’s uniquely good. If even half of the seeming benefits it seems to be showing in early stages right now turn out to be true, it is.
> I assure you it's more than "many conditions downstream of [...]", unless you want to concede that mental health like depression and dementia are related to gut bacteria, then we can be friends.
You have no way to assure that and haven't even made that assertion. Depression and dementia are absolutely related to digestion, gut bacteria (as you mentioned), metabolism, and hormones, all of which are affected by GLP-1s.
Also, if someone starts taking GLP-1's (which has a placebo effect to begin with), loses weight, exercises more, and sees improvement in their diabetes, why wouldn't they also see improvement in their depression?
This is specifically a study on people with HIV-associated lipohypertrophy, which is associated with accelerated aging. Not clear what this would mean for people generally.
The underlying mechanisms (reduced inflammation, improved fat distribution, better metabolic health) aren't unique to that group
They address this and state that there is no reason to believe it wouldn’t also apply to the general population who do not have lipohypertrophy
However they have no evidence of this. While I would expect this to be the case (as a researcher of ageing epigenetics), this is entirely conjecture.
True enough, but many studies show that calorie restriction reduces effects of aging
Not really applicable in humans. Effect is smaller than in mice, and requires some pretty drastic restrictions that aren't exactly pleasant.
The thing with ozempic is that is seems to do several things, most (all?) of them good for us in different ways. We probably just lucked out. It's not the only case - plenty of drugs do incredibly good things with only reasonable side effects. Antibiotics. Ibuprofen. Aspirin. Vitamin D.
A recent example - statins used to be seen as a tradeoff: you get better cardiovascular health, but some hepatotoxicity. Nope, it was wrong - they actually protect your liver. I think the official change came out this year, when I started them a couple of years ago I still found it framed as a side effect.
Statins change some peoples personalities
https://www.bbc.co.uk/future/article/20200108-the-medication...
People on ozempic certainly look more like the crypt keeper than a younger version of themselves. You lose all that buccal fat that defines your young adult face.
Or that's who you notice. My husband takes ozempic for type 2 diabetes and it completely fixed his blood sugar while causing very moderate weight loss.
What the people in this study have causes abnormal visceral fat accumulation in the belly and back and itself causes disturbing changes in body shape and appearance, does not respond or normal weight loss, and hasn't had real treatment options. That ozempic has beneficial effects for it in an RCT is actually awesome, it's the framing given by the headline that is bad.
Any means of attaining weight loss at a similar rate will tend to do the same thing. Especially if you’re starting from quite-heavy, not just dropping 20lb or something.
I notice it in people who have never been the weight that they're suddenly walking around as, with them it often looks overdone, too thin for their features etc, but in those who have used it to get back to weights where I've seen them before...I didn't guess. They had to tell me.
I've lost weight the natural way and people will tell me the same thing. People are just rude to fat people
I wonder how much of that is losing weight too fast and having floppy skin because of it.
It varies. People are often thinner in their twenties than their thirties and forties. If you browse some before and after pictures the ones who have had their skin tighten tend to look younger for that reason alone.
That's just what happens when you get skinny. People who have always been skinny just look sickly always so we don't notice.
This isn’t really surprising at all IMO, but it’s nice that it’s been confirmed.
> “The researchers believe semaglutide’s anti-aging properties stem from its effects on fat distribution and metabolic health. Excess fat around organs triggers the release of pro-aging molecules that alter DNA methylation in key aging-related genes. By reducing this harmful fat accumulation and preventing low-grade inflammation - both major drivers of epigenetic aging - semaglutide appears to create a more youthful biological environment.“
In other words, being medically obese ages your body quite a bit, its stresses out your body with inflammation, etc. Taking Ozempic helps people lose weight, which also reduces inflammation. This is sort of like saying we proved rain (usually) increases humidity lol. A very obvious finding.
The article even says “ Randy Seeley from the University of Michigan Medical SchoolView company profile expressed little surprise at the findings” :)
Yeah this is pretty much a nothingburger. I guess being fat causes biological damage similar to aging, and losing weight (which Ozempic helps with) reverses the process.
Yeah, it looks like it's basically just saying:
1) Being fat is really bad for you 2) Moderate calorie restriction may have some health benefits
Both of which we already knew, the second one being a bit more controversial but a hypothesis that has been around for decades
I think it's controversial mostly because it is mixed in with morality, self-image, personal freedom etc.
I think everyone has the right to be fat, if they have chosen to prioritise other aspects of life, but I think people should be informed and consider the "being fat can be healthy" movement to be quite disingenuous. Do what you want, but be realistic about it, and tricking people into ignoring the negative effects is not fair to them either.
Yeah it's clearly wrong, being fat is not healthy. There are multiple mechanistic explanations for why it might not be healthy (inflammation, hormones etc.), coupled with epidemiological evidence that obese people have massively higher rates of all sorts of health problems.
Note that these results probably apply to Mounjaro/Zepbound as well, because they are the most effective GLP1s on the market right now:
https://glp1.guide/content/semaglutide-vs-tirzepatide-clinic...
My bet is on the reduction in inflammation -- it's a notoriously beneficial positive side effect of GLP1 Receptor Agonists, along with the obvious reduction in weight or HbA1c.
Worth noting: the anti-aging effects may be a byproduct of improved metabolic and inflammatory profiles, not magic cellular rejuvenation
If you think Ozempic (Semaglutide) is good, Retatrutide is going to blow it out of the water:
https://glp1.guide/content/a-new-glp1-retatrutide/
Currently the only people experimenting with it are the underground gray market peptide enthusiasts (you can find them on reddit and elsewhere), but the results are quite intense.
[EDIT] Just to be clear, gray market Retatrutide is illegal, I'm not encouraging you to buy it or do even take GLP1s in general. The point is that we have a preview of anecdata from people (with obviously high risk tolerance) taking this drug.
If Eli Lily is the only producer, how is the gray market being supplied? This makes no sense...
That being said, I'm waiting for oral GLP1 agonists. Injections are a hassle and gray market ones even more so
> If Eli Lily is the only producer, how is the gray market being supplied? This makes no sense...
It turns out enterprising chemists and pharmacists are capable of reverse engineering.
I don't think it's that hard to figure out how someone might do it -- imagine having to reverse engineer food you've received, given many samples. Imagine some of those samples might have "fallen off the back of a truck".
> That being said, I'm waiting for oral GLP1 agonists. Injections are a hassle and gray market ones even more so
This is really going to be the second leg of adoption and will catapult GLP1s even further IMO. Rybelsus has not really seen a ton of popularity compared to the injections. That said, Orforglipron is Eli Lilly's upcoming oral GLP1 and it looks to have really good results:
https://glp1.guide/content/updates-from-maritide-orforglipro...
Wikipedia has the exact formula: https://en.wikipedia.org/wiki/Retatrutide
Why use something which appears to have very similar results to tirzepatide/mounjaro but hasn’t been used by tens of millions on people without obvious issues like tirzep?
Well there's no reason, except it's even more effective.
And 100%, using Retatrutide right now is illegal/not a good idea. It is super risky.
That said, anecdata from people with that risk tolerance is certainly worth looking at.
What's the difficulty level of obtaining Retatrutide through non traditional channels?
It's completely illegal -- the drug is not for sale, obviously is not FDA approved, and is not manufactured anywhere, the only safe/legal way to get it is a via an ongoing trial:
https://trials.lilly.com/en-US/trial/580035
As one might imagine though, capitalism found a way. A LOT of compounding pharmacies are now very good at manufacturing GLP1s (not necessarily the case that the knowledge transfers, but I imagine networks/knowledge sharing groups do), so gray market has sprung up to supply adventurous people with Retatrutide.
I don't know about how hard it is to manufacture GLP-1 agonists specifically, but there's an existing enormous grey/black market for peptides for bodybuilding.
It started in the 90s with synthetic GH and since then the number of research peptides has exploded, all of which are readily available on the grey market.
So all the infrastructure for producing and distributing peptides was already there before GLP-1s were a thing, which probably explains why it didn't take long
Why is it illegal? Are drugs illegal by default or has it been specifically controlled/scheduled?
I looked up which drugs are scheduled in the UK and found the list is about 100x longer than I thought it was and in fact the government don't even publish a definitive and exhaustive list of all substances.
At least in the UK, drugs are legal by default in the sense that a specific chemical has to be classified under the misuse of drugs act to be a "drug".
However, specific classes of drugs (synthetic cannabinoids and substituted phenylethylamines etc.) are banned in their entirety by designer drug legislation. This is to stop people producing stuff like mephedrone etc., because there's an almost endless potential for minor chemical substitutions while still retaining the effects.
AFAIK peptides are not covered by any of that legislation, so they are a grey area, hence why they get sold as "research chemicals" "not for human use" etc. Separately it's probably illegal to produce patented drugs like semaglutide through non-official channels, but that would be a civil/commercial matter, not a drugs offence per se
Well for one they're flying in the face of the patent protection in place for Retatrutide -- that said the legalities around distributing prescription drugs or unknown chemical substances is murky (hence "gray" market).
difficulty level: google search
The gray market stuff makes me nervous
No need for trials, just inject it now!
I'm incredibly interested -- it's just not legal yet, and the drug is in trials by Eli Lilly:
https://trials.lilly.com/en-US/trial/580035
Just to be very explicit here, my profit incentive is selling newsletter subscriptions not selling drugs, if that was the worry.
The thing is that we just won't get any high quality data from the official trials for a very long time, but it looks like it's going to be even better than Tirzepatide which is the current king.
Outside of being simply well-researched, the best thing about GLP1s is that they are safe enough to be taken by millions of people (and they are) -- so anecdata is valuable. It's valuable to know what the "first adopters" are doing and what they're finding and what trends show up there.
[EDIT] Maybe I'm reading the comment wrong -- to answer with good intent assumed, I think GLP1s are basically the answer to obesity on any reasonable time frame.
GLP1s not the answer we wanted (most people would have preferred better food ingredient regulation, more people choosing healhtier lifestyles, etc), but it's the solution we're getting, it seems like.
Right now the only thing I think most can do to help this wave along (unless you're a drug manufacturer, insurer, or politician) is to share as much information as possible on positive and negative side effects, how the drugs work, why they work, etc.
[EDIT2] - Clearly there was no positive intent. I guess it's my own fault I took the time to seriously respond.
The original comment (now edited) was a question about me seeming like a disinterested third party and asking why I am discussing a gray market drug.
Doesn't biological age normally go down with weight loss? Is it just a corollary of the off-label effects of the drug?
It's not that it's going down, the article suggests that it slows.
If I lose 20 kilo's, my "biological age" might go down 2 years, but that doesn't mean it's "slowed"
Slowing in this context means going down. Basically they look at 'age acceleration', I.e. how old are you epigentically compared to chronologically. They saw a reduction of several years in this measure over a much shorter period, basically meaning their epigenetic ages went down.
Although one of the clocks they used, DunedinPACE, only looks at pace of ageing, so in that case you can only infer that it slowed (as you do not get an 'epigenetic age' figure from DunedinPACE).
I was wondering a similar thing - even as simple as wear-and-tear on your joints, hips and back is less as a smaller bodyweight. I notice I even look younger at a lower bodyweight (up to a point)
It’s so fascinating that we just keep on finding more positive effects.
They are all downstream from obesity; so it’s obvious from that standpoint since obesity is so dangerous.
We also like to keep track of all the bad ones too[0] (tl;dr they're actually pretty reasonable).
It's amazing what lowering inflation, reducing body weight can do to the body. It's almost becoming irrelevant that GLP1 Receptor Agonists were originally for type 2 diabetes (i.e. reducing HbA1c) -- the effects are profound. Kidney health, heart health, overall health, longer lives -- all for the low low cost of gastrointestinal problems (which can be serious, especially if dehydrated).
[0]: https://glp1.guide/content/are-glp1-side-effects-all-the-sam...
Is the term "biological age" even well defined?
Presumably it is in the narrow context of the study, since they need something they can consistently measure and compare
> The researchers used epigenetic clocks to assess biological aging - sophisticated tools that identify patterns of DNA methylation, chemical tags that affect gene activity and shift predictably with age
I think you're very correct to identify the gulf between what the average MedPath headline reader understands "biological age" to mean, and the very specific chemical tags being measured and reported
Lots of anecdotes and opinions in the thread. Read the post and the science.
Any study which uses epigenetic clocks can be discarded. There is to my knowledge no test which produces reliably measurements which don't have big error bars. The only conclusion this study can really make is: Ozempic changes the 'thing' which the epigenetic clock test also measured.
it does seem that there is no reliable connection with "epigenetic clocks" where people are shown to be dying at the same bio age, regardless of calender age......all of the mortality estimating calculations rely on many "factors", so the "ozempic" effects will be just part of a puzzle, where I will bet anything that attitude, demenour, , basic personal conduct will weigh in as the hinge pins that everything else pivots around..........stress, and how that is delt with, and anyone who thinks that one compound is going to reset the whole clock on a complex organism is kidding themselves, which if done right, works ;) so....it's all for the good
It it ozempic specifically or just the side effect of eating less (which also has tons of evidence for extending life)?
Are we close to having generic semaglutides e.g. available in India? Or locked into high prices for the foreseeable future?
Generic Semaglutide is already produced on a massive scale throughout the world. However, it is unlawful to import and sell and will remain so until 2032 in the USA.
In other markets, where it is under patent, it is significantly cheaper than the $500/month or more in the US currently. For example in the UK it is roughly $150/month USD privately (i.e. not through the NHS).
In China it will be out of patent within two years.
There's a whole little online subculture of people in the US importing the precursors and making it themselves at home for dirt-cheap.
I gather it's extremely easy and basically fool-proof, as far as producing the desired drug and not producing some other, undesired drug. Much easier than, say, home-brewing beer. The risk is all in contamination, which presents a vector for infection.
[EDIT] I don't mean to downplay the risks or suggest people go do this, only to highlight that there's enough demand for this that we're well into "life, uh, finds a way" territory, and also just how lucky (assuming these hold up as no-brainers to take for a large proportion of the population) we are that these things are so incredibly cheap and simple to make, if you take the patents out of the picture.
Not just the current generation of drugs, but they also import and use the next generation that is still in clinical trials and won't be on the market for at least a year. I had it reccomended to me online in a very casual as if it were a supplement. The risk with the is not just contamination but also if you get side effects there's no recourse to sue because you bought it from a chemical factory in China. The new generation of glp peptides is similar to the old one, but still can have unintended side effects as they do work on three receptors rather than the two that the current generation does
Iirc, that pricing will change in the US as Trump will require that the price of drugs to Medicaid patients must match or be less than that of any other developed nation.
Since about 1/4 of the people in the US are on medicaid, close to 90 million, that means the drug manufacturers will probably raise the price for everyone else in the US because they got to get their profits somehow...
https://www.whitehouse.gov/fact-sheets/2025/07/fact-sheet-pr...
Unfortunately, per the link, it sounds like a voluntary arrangement. Essentially they're asking drug companies nicely to stop ripping off Americans.
If they're serious about this, they would introduce legislation rather than send strongly worded letters to pharma companies.
In a recent podcast[0], Ben Bikman explained some of background and pitfalls of GLP-1 drugs. When the drugs were first prescribed, dosages were much smaller than the dosages now prescribed for weight loss. Microdosing might be a better and safer strategy.
The podcast is only 3 hours long! The GLP-1 discussion starts at 2:09:53.
[0] https://www.foundmyfitness.com/episodes/ben-bikman
EDIT: ycopilotFYT version https://www.cofyt.app/search/dr-ben-bikman-how-to-reverse-in...
It's not GLP-1's in particular, it's protective effects of manifold evolutionary adaptations to semi-regular caloric deficits. Cancer and CHD go way, way up with Westernized diets.
I just started taking zepbound and I went from binge eating 2-3 times a day to eating half a meal overnight.
I've already lost 12 pounds (6% of my bodyweight) in a week, which is definitely too much, but I was full of salt. I basically pickled myself.
The side effects are quite stark. My stomach feels paralyzed. I became anorexic (again) overnight
It remains eye opening to see how much losing weight does to people.
Be very cautious with these miracle drug headlines. There's a strong financial incentive to highlight only the good news.
My mother, a healthy and active 87-year-old, started taking Ozempic because she was overweight and her doctor was impressed by the drug’s supposed miracles. She ended up suffering from severe intestinal motility issues, went through a lot of pain, and had to be admitted to the ICU.
The long-term systemic effects of these drugs are still largely unknown.
> The long-term systemic effects of these drugs are still largely unknown.
The long term effects of obesity are very well known though and unlikely to be better than any still unknown negative effect semaglutide might have.
Haven’t these types of drugs been in use for ~15 years?
> Haven’t these types of drugs been in use for ~15 years?
The predecessor of semaglutide, liraglutide has been sold since 1998. GLP-1 has been studied since the 70s. The first human was injected with GLP-1 agonists in 1993 IIRC.
Further, Ozempic itself is nearly 10 now and some people have been on Exenatide for 20+ years continuously now.
These drugs are not novel, or new and we absolutely know the long term health impact.
20 years isn't a lot of time
Maybe don’t give them to grandma? Idk man but at 87 anything that happens might as well have been the grim reaper deciding it was their time.
You don't think her being 87 might have something to do with her complications?
It is a well Mongolian effect of Ozempic.
She stopped using the drug and the problems disappeared.
Well also short term complications don't imply long term complications.
If you're allergic to peanuts it doesn't mean everyone is going to suffer some huge medical crisis from peanuts in 20 years.
I can't open this link but I wonder if the weight loss or the medicine itself is performing the anti-aging
I was just researching this myself before investing in LLY.
For cardiovascular health, they see benefits even with people who are at a healthy BMI, which suggests therapeutic effects beyond just losing weight.
it could also suggest that BMI isn't a great metric, though, as has been in the news often lately.
regardless, thanks too.
It isn't. Waist-to-height ratio is a much better predictor of cardiovascular issues - you want to stay below 0.5.
I never went above 25 BMI but I wouldn't call myself a healthy person as it's obviously like that only due to low muscle mass.
Very interesting! Thanks for chiming in.
I know why people hate Ozempic. It is because it devaluates struggle and voids moral superiority of those who did keep themselves from becoming obese by self-restriction before: now these people feel like fools because all of a sudden, everyone is becoming slim, and the advantage of being slim disappears. They naturally question how is it fair. Well, life's not fair.
That's if people think obesity is just the individual's fault. In nutrition there's a distinction between psychology factors, the environment (called the obesogenic environment), genetics, social factors, etc. If you live in the US it must be really hard to avoid being overloaded by food, so I think the real angry group of people will be companies, not being able to force people to eat more, I welcome that!
I hate ozempic because I have no reason to be prescribed it and if it has these anti aging effects or improves self control with other vices, I'm missing out and the ex-fatties will all live longer than me
Sadly it seems to have very little effect in these domains on non-overweight people. In studies, on large groups, Ozempic helps people quit drinking a lot better than it helps quitting smoking - because alcoholics tend to be overweight but smokers tend to be skinny. The higher was someone's BMI, the more pronounced are ALL of the semaglutide effects, even those not apparently associated with weight at all.
Fasting is good. I do it without medicines and crap. 24h-48h fast. Skip meals. BMI back to 19 and it feels GOOOOD BABYYY.
There is another study that comes to mind.
https://www.pnas.org/doi/abs/10.1073/pnas.2420092122
I have no idea why you're down voted. The replication crisis is real, and it is well known that fraud is a part of it
Maybe because that is a whole different topic that is only tangentially related to this thread?
Because it's a content-free dismissal. No attempt is made to link it to this study in particular.
If the poster had said
"given the replication crisis and outright fraud endemic in scientific publications these days, I have little faith that this research will bear fruit for the general population"
Would that have been specific enough?
what would be reversing biological age from regular running and eating chicken breast + veggies with olive oil.
You can tell if that regime reverses aging when you instead start wanting to eat chicken nuggets and mac & cheese.
Nice.
Wish I could run. Knee says no.
Do you have an injury? Knees over toes exercises can do wonders for rehab. From a form perspective, it also helps to avoid heel-striking.
Please stop with these obvious pharma ads, nobody needs to take Ozempic! Change your lifestyle and most importantly: STOP EATING JUNK FOOD
It really puzzles me how people would just pop a pill instead of make some lifestyle changes. Maybe it's just my personality type, but it disturbs me how most people just want something quick and easy instead of doing the actual work and becoming overall better via a real learning journey by struggling through changing bad habits.
But whatever, they do whatever works for them! I don't like pharma.
But junk food is fun: Maybe we can eat junk food, have fun in life, and still be reasonably healthy, with the help of science
(and if glps don't work well enough to allow this, then maybe the next medicine in the pipeline)
The drug just makes you eat less.
I guess maybe I'm one of the few who consider "reversing 3.1 biological years" to be a personal insult. Something that polled well in a group of pre-kindergarteners. What happened, some statistical bloodwork metric was tortured to produce such a claim? A mouse population survived the lab a little longer?
Here's an article that answers your question [1]. It in the second bullet point near the top.
[1] https://trial.medpath.com/news/5c43f09ebb6d0f8e/ozempic-show...
Yes, epigenetic clocks discovered in 2010 and even the researcher who discovered them might feel insulted by the phrase of a prescription drug declaring "reverse biological aging 3.1 years"
If you're really interested in that and not just trolling, these are the measures used by the study:
After adjustment for sex, BMI, hsCRP, and sCD163, semaglutide significantly decreased epigenetic aging: PCGrimAge (-3.1 years, P = 0.007), GrimAge V1 (-1.4 years, P = 0.02), GrimAge V2 (-2.3 years, P = 0.009), PhenoAge (-4.9 years, P = 0.004), and DunedinPACE (-0.09 units, ≈9 % slower pace, P = 0.01). Semaglutide also lowered the multi-omic OMICmAge clock (-2.2 years, P = 0.009) and the transposable element-focused RetroAge clock (-2.2 years, P = 0.030).
I guess Ozempic face is what "anti-aging" looks like? Nothing to see there lol. The backlash on GLP-1s is gonna make thalidomide look like penicillin.