I’m unsurprised that a large component of the treatment is effectively just “lose weight”. For many years I’ve heard accounts of significant weight loss reversing type 2 diabetes.
I wouldn't ignore the effect that having surgery and then two weeks of a strictly controlled food intake has. That might account for a large proportion of the success rate. I heard about a study that found that the fasting required for bariatric surgery actually provides a large proportion of the benefit of the procedure.
If you catch type 2 diabetes before it gets so bad that it has killed off the beta cells, then your best treatment is to fast for a while. After a couple of days, you should notice a massive improvement in glucose control. A week of fasting a couple of times a year might be all it takes to give you a complete cure. YMMV, but in my opinion (and that of a whole load of people who know what they're talking about) it's better than filling yourself with drugs.
After the beta cells have been killed off by overwork, yeah, you need insulin. But you can still reduce the amount you need by losing weight.
For type-2 diabetes, various forms of dietary therapy such as nutritional ketosis have proven extremely effective in reducing or even eliminating many patients' need for exogenous insulin. But we usually refer to that as putting the condition into remission rather than a "cure".
I was diagnosed with type 2 diabetes about two and a half years ago. After doing some research, I put myself on a strict keto diet. Within about a month, my A1C went from over 13 to hovering around 6 and has stayed there. Never took any diabetes medication.
I do give myself a "vacation" from the diet about once a month, which I usually reserve for a special occasion.
Do you find that this requires an unusual amount of self-control? I have no reason to manage my food intake, but in the limited times where I have I've found it quite difficult
There is a study running for this in the UK currently [0], and I expect there are worldwide studies running now. This is the time for those interested and eligible to register. But for the rest of us, the treatment seems to be inevitable now. The question is how long until it's proven safe, the red tape is cut through, and it enters the market. I would speculate, unless something catastrophic happens, it should be available within 10 years.
No doubt, the current T1D market players will have created some legal moat, so it might be best for the patients if these companies are the ones to bring the treatment to the market. But we shall see - the current big pharma in diabetes space is heavily invested in drug production rather than implantation procedures. It is a very different business model requiring very different facilities, management, and technology.
Immunology & autoimmune attack is still a wild country where discoveries are being made regularly and only a handful of people have even a rough grasp of the terrain.
Most people with T2D do not take insulin, it's only useful if your body cannot make a sufficient amount. In my case I have no need for it, the cells became resistant to the effects of insulin. 25% is probably a decent estimate.
> Recellularization via electroporation therapy (ReCET) is a novel endoscopic procedure that uses electroporation to induce cellular apoptosis and subsequent reepithelization.
GLP-1s baseline eliminate insulin for about ~40% of people. This boosts that number to 86%.
Note that Tirzepatide also reduces the chance of developing type 2 in the first place by 94%, and I suspect that newer generation receptor agonists will see higher insulin discontinuation rates in general.
Very cool stuff all around. Might finally be able to put this whole obesity-and-diabetes thing to bed.
The side effects are wildly exaggerated due to the current social media discourse on the subject.
I am in a pretty close knit community of 100s of people on the subject and while the side effects should not be discounted, figuring out ways to properly take the medication more or less eliminates them completely for nearly everyone.
The current dosing and schedules of the drug (and all GLP-1s for that matter) are largely an effect of what was tested during trials and not what will end up being most effective a decade from now. The rest of it is patient compliance and liability from drug manufacturers.
The most obvious two things to point at are that the half life of Tirzepatide is 5 days while the prescriptions are for 7 day intervals for ease of use. The other would be the rather large jumps in dosing (2.5mg per step) available in injector pen forms and prescribed.
Some bleeding edge doctors are willing to take the risk to go outside dosing and schedule guidelines, but not many.
Even then, the side effects seem to be rather minor compared to obesity or T2D and few and are far between.
I also had similarly reactions to the topic before I started to really look into it and dig deeper. I firmly believe these medications will change society at a level only antibiotics have so far.
I worked in pharmaceutical development and absolutely agree on the labeled dosing point. When each arm of your study costs X00 million dollars and Y years, you dont optimize dosing intervals. Moreover, there is no global optimum due to biologic variability in patients. Some patients are flat out non-responders, and some tolerate dosing intervals 10X the average.
That said, there is nothing magic about aligning the half-life and interval. 50% isn't a minimum concentration threshold for efficacy. depending on the product, it can be anything. Sometimes area under the curve is the relevant parameter. Sometimes you want the product to go under a limit before redosing.
The one part I disagree with is about bleeding edge doctors. Maybe it is my field, but I find doctors to be readily willing to completely ignore the labeling. Statutory protections are high for clinicians operating off label. If someone is interested, I suggest they raise it with their doctor. For most medications, the dosing is far from the individual optimum.
The side effects are usually short lived. I'm on tirzepatide and had some mild digestive issues for the 1st 3 - 4 weeks and haven't had any since then. My side effects when starting metformin were worse.
Directionally each generation of these drugs targets more receptors and has fewer side effects. Tirzepatide is also amazing in that people lost an average of 20.9% of their body weight in studies. [1]
Tirzepatide does not force you to lose weight, it makes it much easier to stick to your diet. Maybe too easy, since people who are not prepared to manage their diet may find themselves missing meals accidentally (lots of stories of people losing more than 2 pounds a week, which is very satisfying when it happens but not the healthiest way to drop weight).
Make sure you are getting sufficient calories and you won't lose any weight.
The caveat is that it slows digestion down and this effectively reduces your capacity to eat a lot of food. So maintaining a high calorie diet may require some changes to increase the energy density of your food.
> lots of stories of people losing more than 2 pounds a week, which is very satisfying when it happens but not the healthiest way to drop weight
Folks should follow medical advice and do what works for them, but be aware that these guidelines were established prior to the obesity epidemic. I’d be highly surprised if someone weighing 300lbs vs. the same person weighing 190lbs should be losing weight at the same rate per week.
I imagine these will be updated to be body weight (or fat) adjusted as time goes on, like some doctors are already doing.
How long does this cure last until the unhealthy diet & lifestyle that originally caused the insulin resistance bring it back again?
It's frustrating, as Type 2 diabetes is 100% manageable through diet. You don't even have to exercise, just eat healthy. Today, with the use of continuous glucose monitors, you have all the data you need to make informed diet decisions - you know exactly what "eat healthy" means for your body.
Not sarcasm: I'm sure it would be frustrating to see so much scientific and commercial effort going into treating TIID pharmacologically when you believe the solution is trivial. But you could also consider all of these developments as evidence that the prescription of "just eat healthy" isn't broadly useful.
When you say "it's a modern cultural problem", do you mean, as most people appear to mean, "This is not a social problem worth solving, these people deserve it for their moral failings, and their death is a useful example for the rest of us"?
Most people don't actually say it out loud, but this is all directly implied by the "personal responsibility" retort that is wildly popular among people who don't actually suffer from a given malady, in response to attempts to address it collectively.
not OP, but I agree it is modern cultural problem and a personal responsibility problem.
However, I dont agree with your supposition from that.
I think that obesity is a symptom of a cultural problem worth solving, not an individual moral failing, and there are better ways to learn than death.
There are lots of things in our culture that result in physical and mental sickness. It is good to treat the symptoms, but we should also pay attention to the cause.
Culture operates both at the individual and collective level. One can not exist without the other. One can not change without changing the other. Personal beliefs and actions shape collective culture, and culture shapes personal beliefs.
Friendly fwiw: Your parent clearly does not think it is a "modern cultural problem":
> "when _you_ believe the solution is trivial" (emphasis mine)
They were trying to start a polite dialogue with you by displaying that they could see things from your purview. Probably with the hope of building common-ground that would, in turn, invite you to maybe see the other side:
GLP-1 drugs don’t make you burn fat, they make you eat healthy (or healthier, at least). That’s why they’re so amazingly effective and the reason why is even more amazing - they hack your reward subsystem.
GLP-1 drugs seem to increase resting heart rate. I suspect that also increases total daily energy expenditure, although I don't know that we have reliable data on that yet.
That can happen, but is not universal. My resting heart rate has been dropping (probably in lock step with my weight), it has not risen one bit since I started taking tirzepatide. And my heart rate variability has been trending up, not down.
> But you could also consider all of these developments as evidence that the prescription of "just eat healthy" isn't broadly useful.
As programmers, we usually prefer to remove code to fix a bug than adding patches on top of buggy code. Let's not pretend that the same logic does not apply here.
That's clearly double unhealthy behavior and will bring unintended consequences. Which might be better than the current predicament but still let's not pretend this is not a "monkeypatch".
Considering the article mentions ReCET and semaglutide, presumably most people in the study weren't resuming the unhealthy diet.
Semaglutide is ozempic. By itself it can be enough to help people get their A1C down through healthier diets.
For me to find the study especially interesting, I'd have to see a comparison between ReCET + semaglutide vs just semaglutide. And upon re-reading I see that's their plan.
> “We are currently conducting the EMINENT-2 trial with the same inclusion and exclusion criteria and administration of semaglutide, but with either a sham procedure or ReCET. This study will also include mechanistic assessments to evaluate the underlying mechanism of ReCET.”
s/Broken ankles are 100% manageable by not walking where you could slip and fall. If only today's society made informed decisions about their walking habits, we wouldn't need all these artificial casts and surgeries. How long does a cured ankle last till the lifestyle of walking around breaks it again?/
I’m unsurprised that a large component of the treatment is effectively just “lose weight”. For many years I’ve heard accounts of significant weight loss reversing type 2 diabetes.
I wouldn't ignore the effect that having surgery and then two weeks of a strictly controlled food intake has. That might account for a large proportion of the success rate. I heard about a study that found that the fasting required for bariatric surgery actually provides a large proportion of the benefit of the procedure.
If you catch type 2 diabetes before it gets so bad that it has killed off the beta cells, then your best treatment is to fast for a while. After a couple of days, you should notice a massive improvement in glucose control. A week of fasting a couple of times a year might be all it takes to give you a complete cure. YMMV, but in my opinion (and that of a whole load of people who know what they're talking about) it's better than filling yourself with drugs.
After the beta cells have been killed off by overwork, yeah, you need insulin. But you can still reduce the amount you need by losing weight.
For type-2 diabetes, various forms of dietary therapy such as nutritional ketosis have proven extremely effective in reducing or even eliminating many patients' need for exogenous insulin. But we usually refer to that as putting the condition into remission rather than a "cure".
https://doi.org/10.1530/EDM-22-0295
This.
I was diagnosed with type 2 diabetes about two and a half years ago. After doing some research, I put myself on a strict keto diet. Within about a month, my A1C went from over 13 to hovering around 6 and has stayed there. Never took any diabetes medication.
I do give myself a "vacation" from the diet about once a month, which I usually reserve for a special occasion.
Do you find that this requires an unusual amount of self-control? I have no reason to manage my food intake, but in the limited times where I have I've found it quite difficult
I need someone who control his type 2 diabetes with the ornish diet which is fat vegetarian no sugar or simple carbs...
And maybe the secret is the no sugar nor simple carbs
Note: This is about diabetes type 2, not type 1. Might be worth to editorialize the heading in this case.
eh, I had a brief glimmer of hope
As a T1D I empathize so strongly with this comment.
There was a promising example in China where Scientists cured a single woman who had T1D. It's n=1, but the first step to a cure is curing someone :)
Source: https://www.nature.com/articles/d41586-024-03129-3
There is a study running for this in the UK currently [0], and I expect there are worldwide studies running now. This is the time for those interested and eligible to register. But for the rest of us, the treatment seems to be inevitable now. The question is how long until it's proven safe, the red tape is cut through, and it enters the market. I would speculate, unless something catastrophic happens, it should be available within 10 years.
No doubt, the current T1D market players will have created some legal moat, so it might be best for the patients if these companies are the ones to bring the treatment to the market. But we shall see - the current big pharma in diabetes space is heavily invested in drug production rather than implantation procedures. It is a very different business model requiring very different facilities, management, and technology.
[0] https://www.diabetes.org.uk/our-research/get-involved/take-p...
Immunology & autoimmune attack is still a wild country where discoveries are being made regularly and only a handful of people have even a rough grasp of the terrain.
n=3 but the other two haven’t been monitored for a year yet. Promising.
Something that works for 95% of people with diabetes then. Fantastic!
They really should be called different names. The diseases are really not all that similar other than (sometimes) the need to take insulin.
Don't only something like 25% of type 2 diabetics take insulin?
Most people with T2D do not take insulin, it's only useful if your body cannot make a sufficient amount. In my case I have no need for it, the cells became resistant to the effects of insulin. 25% is probably a decent estimate.
Paper: https://pubmed.ncbi.nlm.nih.gov/38692517/
> Recellularization via electroporation therapy (ReCET) is a novel endoscopic procedure that uses electroporation to induce cellular apoptosis and subsequent reepithelization.
... plus GLP-1.
GLP-1s baseline eliminate insulin for about ~40% of people. This boosts that number to 86%.
Note that Tirzepatide also reduces the chance of developing type 2 in the first place by 94%, and I suspect that newer generation receptor agonists will see higher insulin discontinuation rates in general.
Very cool stuff all around. Might finally be able to put this whole obesity-and-diabetes thing to bed.
Tirzepatide side effects sound pretty nasty, though less so than dying in a diabetic coma.
https://en.wikipedia.org/wiki/Tirzepatide
The side effects are wildly exaggerated due to the current social media discourse on the subject.
I am in a pretty close knit community of 100s of people on the subject and while the side effects should not be discounted, figuring out ways to properly take the medication more or less eliminates them completely for nearly everyone.
The current dosing and schedules of the drug (and all GLP-1s for that matter) are largely an effect of what was tested during trials and not what will end up being most effective a decade from now. The rest of it is patient compliance and liability from drug manufacturers.
The most obvious two things to point at are that the half life of Tirzepatide is 5 days while the prescriptions are for 7 day intervals for ease of use. The other would be the rather large jumps in dosing (2.5mg per step) available in injector pen forms and prescribed.
Some bleeding edge doctors are willing to take the risk to go outside dosing and schedule guidelines, but not many.
Even then, the side effects seem to be rather minor compared to obesity or T2D and few and are far between.
I also had similarly reactions to the topic before I started to really look into it and dig deeper. I firmly believe these medications will change society at a level only antibiotics have so far.
I worked in pharmaceutical development and absolutely agree on the labeled dosing point. When each arm of your study costs X00 million dollars and Y years, you dont optimize dosing intervals. Moreover, there is no global optimum due to biologic variability in patients. Some patients are flat out non-responders, and some tolerate dosing intervals 10X the average.
That said, there is nothing magic about aligning the half-life and interval. 50% isn't a minimum concentration threshold for efficacy. depending on the product, it can be anything. Sometimes area under the curve is the relevant parameter. Sometimes you want the product to go under a limit before redosing.
The one part I disagree with is about bleeding edge doctors. Maybe it is my field, but I find doctors to be readily willing to completely ignore the labeling. Statutory protections are high for clinicians operating off label. If someone is interested, I suggest they raise it with their doctor. For most medications, the dosing is far from the individual optimum.
The side effects are usually short lived. I'm on tirzepatide and had some mild digestive issues for the 1st 3 - 4 weeks and haven't had any since then. My side effects when starting metformin were worse.
Directionally each generation of these drugs targets more receptors and has fewer side effects. Tirzepatide is also amazing in that people lost an average of 20.9% of their body weight in studies. [1]
[1] https://www.nejm.org/doi/full/10.1056/NEJMoa2206038
What if I didn't want to lose weight? Would I be a bad candidate?
Tirzepatide does not force you to lose weight, it makes it much easier to stick to your diet. Maybe too easy, since people who are not prepared to manage their diet may find themselves missing meals accidentally (lots of stories of people losing more than 2 pounds a week, which is very satisfying when it happens but not the healthiest way to drop weight).
Make sure you are getting sufficient calories and you won't lose any weight.
The caveat is that it slows digestion down and this effectively reduces your capacity to eat a lot of food. So maintaining a high calorie diet may require some changes to increase the energy density of your food.
> lots of stories of people losing more than 2 pounds a week, which is very satisfying when it happens but not the healthiest way to drop weight
Folks should follow medical advice and do what works for them, but be aware that these guidelines were established prior to the obesity epidemic. I’d be highly surprised if someone weighing 300lbs vs. the same person weighing 190lbs should be losing weight at the same rate per week.
I imagine these will be updated to be body weight (or fat) adjusted as time goes on, like some doctors are already doing.
I didn’t seem to get this from the article but this this involve taking semaglutide for the rest of your life or the diabetes returns?
How long does this cure last until the unhealthy diet & lifestyle that originally caused the insulin resistance bring it back again?
It's frustrating, as Type 2 diabetes is 100% manageable through diet. You don't even have to exercise, just eat healthy. Today, with the use of continuous glucose monitors, you have all the data you need to make informed diet decisions - you know exactly what "eat healthy" means for your body.
Not sarcasm: I'm sure it would be frustrating to see so much scientific and commercial effort going into treating TIID pharmacologically when you believe the solution is trivial. But you could also consider all of these developments as evidence that the prescription of "just eat healthy" isn't broadly useful.
100% agree, it's a modern cultural problem. We look for drug and technology solutions because "doing the right thing" is hard.
When you say "it's a modern cultural problem", do you mean, as most people appear to mean, "This is not a social problem worth solving, these people deserve it for their moral failings, and their death is a useful example for the rest of us"?
Most people don't actually say it out loud, but this is all directly implied by the "personal responsibility" retort that is wildly popular among people who don't actually suffer from a given malady, in response to attempts to address it collectively.
not OP, but I agree it is modern cultural problem and a personal responsibility problem.
However, I dont agree with your supposition from that.
I think that obesity is a symptom of a cultural problem worth solving, not an individual moral failing, and there are better ways to learn than death.
There are lots of things in our culture that result in physical and mental sickness. It is good to treat the symptoms, but we should also pay attention to the cause.
Culture operates both at the individual and collective level. One can not exist without the other. One can not change without changing the other. Personal beliefs and actions shape collective culture, and culture shapes personal beliefs.
Friendly fwiw: Your parent clearly does not think it is a "modern cultural problem":
They were trying to start a polite dialogue with you by displaying that they could see things from your purview. Probably with the hope of building common-ground that would, in turn, invite you to maybe see the other side: Perhaps reconsider their olive branch?GLP-1 drugs don’t make you burn fat, they make you eat healthy (or healthier, at least). That’s why they’re so amazingly effective and the reason why is even more amazing - they hack your reward subsystem.
GLP-1 drugs seem to increase resting heart rate. I suspect that also increases total daily energy expenditure, although I don't know that we have reliable data on that yet.
That can happen, but is not universal. My resting heart rate has been dropping (probably in lock step with my weight), it has not risen one bit since I started taking tirzepatide. And my heart rate variability has been trending up, not down.
Why do you suspect it changes energy expenditure?
> But you could also consider all of these developments as evidence that the prescription of "just eat healthy" isn't broadly useful.
As programmers, we usually prefer to remove code to fix a bug than adding patches on top of buggy code. Let's not pretend that the same logic does not apply here.
That's clearly double unhealthy behavior and will bring unintended consequences. Which might be better than the current predicament but still let's not pretend this is not a "monkeypatch".
Considering the article mentions ReCET and semaglutide, presumably most people in the study weren't resuming the unhealthy diet.
Semaglutide is ozempic. By itself it can be enough to help people get their A1C down through healthier diets.
For me to find the study especially interesting, I'd have to see a comparison between ReCET + semaglutide vs just semaglutide. And upon re-reading I see that's their plan.
> “We are currently conducting the EMINENT-2 trial with the same inclusion and exclusion criteria and administration of semaglutide, but with either a sham procedure or ReCET. This study will also include mechanistic assessments to evaluate the underlying mechanism of ReCET.”
s/Broken ankles are 100% manageable by not walking where you could slip and fall. If only today's society made informed decisions about their walking habits, we wouldn't need all these artificial casts and surgeries. How long does a cured ankle last till the lifestyle of walking around breaks it again?/
Well, shit. I can't believe it never occurred to these obese people to just eat right!
You, sir, are a modern messiah. Well done.