"Generally, the more weight people regained, the more their cardiovascular and metabolic health improvements reversed."
You don't say ;-) I lost 50 lbs and have kept it off for the past year while maintaining great BP. But I'm under no illusions GLP-1 medications don't have dangers and cause problems for many. It should be handled on an individual basis like any serious medication.
That said, is someone losing a lot of weight then gaining half of it back worse than them just staying where they were? I don't know the answer to that one.
There doesn’t need to be an off-ramp they just have to take it for life. Why would someone think they would keep the weight off? If they could they would have before Ozempic.
Interesting. Saying, "there may not be a safe off-ramp," doesn’t feel quite right. The article describes people losing weight while on the drugs and then regaining weight after stopping them. That's not ideal, but it does imply an off-ramp, just with regressions.
Compare that to something with no real off-ramp: testosterone replacement therapy. Once you're on TRT, you can permanently suppress your body's own testosterone production, and many men won't produce enough on their own afterward.
Plus if you look at the numbers (found in the comments of that story):
17.5% maintained 75+% of their weight loss.
25% maintained 50-75% of their weight loss.
23% maintained 25-50% of their weight loss.
24% maintained 0-25% of their weight loss.
> regained significant amounts of the weight they had lost on the drug [...] blood pressure went back up, as did their cholesterol, hemoglobin A1c [...] fasting insulin
These symptoms will be familiar for anyone who has lost weight dieting and then returned to eating junk food.
Or an alternative title: "36 months of tirzepatide permanently treated obesity in 17.5% of patients."
I think that it is quite unsurprising that without the drug a large amount of people revert to their previous behavior and with that will revert to their previous weight.
> Of the 308 who benefited from tirzepatide, 254 (82 percent) regained at least 25 percent of the weight they had lost on the drug by week 88. Further, 177 (57 percent) regained at least 50 percent, and 74 (24 percent) regained at least 75 percent. Generally, the more weight people regained, the more their cardiovascular and metabolic health improvements reversed.
So weight loss was actually maintained for most people -- the hard part is finding a healthy daily lifestyle which can maintain the drastic effects of GLP1s.
This information isn't new -- weight regain has been studied before and I've written about it before:
The missing piece to this article is just how bad the alternative is -- never having the cardiovascular and metabolic benefits is clearly not the best strategy (and if simply changing patterns was so easy, people would have done it already).
GLP1s don't work for everyone but they're pretty close to miraculous in effect given the balance of positive and negative side effects. Making GLP1s cheaper & more tolerable then figuring out how to actually deal with the complex web of how to keep the weight off sustainably for most people seems like the right way forward here, not avoiding potentially life-saving medication because you may not be able to get off of it as fast as you want (if you can afford it).
BTW, there is already generic Liraglutide, and legal workarounds for getting compounded Semaglutide that already mean no one pays the $1000 that was in the zeitgeist a while ago. Even Lilly Direct and similar outfits from Novo sell for $500/month, with the $150/month pricing coming soon[0].
> So weight loss was actually maintained for most people
Unless I'm mistaken, how can you interpret that from an article that claims that 57-82% of participants regained 25%-50% of their weight loss, with 24% regaining at least 75% of it? In just a bit more than a year and a half, too.
As a GLP-1 user im really surprised that this is newsworthy. The mechanism of how these drugs lead to weight loss is appetite reduction. On GLP-1s -> less appetite, off GLPS-1s -> more appetite. Given the general health benefits that are being observed with GLP1-s the only reason to get off them is costs imo. They are absurdly expensive. Hope this will change in the next 10 years with patents running out and generics being available for cheap. The actual cost of production seem to be quite low. Gray/black market has them available for around a tenth of the otc price.
The body yearns for its prior homeostasis. This is true when you lose weight with a strict diet. It's true when you lose it using a medication.
The struggle doesn't stop when you stop losing. My personal experience was that it takes about 2 years for the new 'normal' to kick in. (I lost 60lbs when I was in my early 20s and kept it off until today. The 'after' period was as taxing as the 'losing' period, but in a different way)
At that point only can you 'relax' a bit around your body's cravings for calories.
It's not the worst thing in the world to be on a medication for a couple years rather than a few months, but long-term study of this class of drugs is certainly warranted and necessary.
It’s no different from people who undergo gastric bypass surgery. Those with food addictions/habits manifest them elsewhere such as gambling, or if they are seriously addicted, they continue to eat which bursts their band.
My wife is back devouring cookies after being on mounjaro for 4 months. Thankfully she lost most weight all by herself so wasn’t totally reliant on the medication. But it’s crazy how noticeable the difference of one’s eating habits when on and off it.
Same is true for: insulin, Levothyroxine, Antiretroviral Therapy (HIV), Enzyme Replacement Therapy ( Pompe Disease or Gaucher Disease, antipsychotic medications for severe schizophrenia. And many others. And here’s the interesting twist, the closer the Number Needed to treat is to 1, the more helpful the medication should be viewed. All these medications have an extremely low NNT, including GLP1s.
Each time an article on glp-1 is out, I will comment:
Yes, you can loose weight without it, I did, I'm even in the healthy range now.
No, you don't have to, if you need medicine help, take it.
When I lost weight, I had my first real job that I liked so much, it didn't felt like one, 11 weeks of vacation per year, a nice enough apartment I couldn't be evicted of, great emotional support and advices and support from a doctor.
The only thing draining my willpower every day was the calorie restriction, and nothing else to worry about.
If you're in a similar spot I was, maybe trying a diet without glp-1 is better since we don't have any long term study on it yet, but if you're not: obesity will destroy your body more than any long term side effects can. Please take them if you can afford it.
The only thing I earned beside uncomfort and pain when I lost weight without drugs are internet points on hacker news, and the ability to say 'i did it' (also glp-1 didn't exist, so less long term health issues from obesity). Honestly if I had to redo it, I would take the drug despite a similar situation. Weight loss is hard, and not being able to do it without help is not an indictment on you or your character, but on your situation.
> "this new class of drugs should be rebranded from “weight loss” drugs to “weight management” drugs, which people may need to take indefinitely."
I suspect the manufacturers view this as a feature not a bug. :-) More seriously, I find the article's conclusions to be pretty much what I'd expect. Most medicines aren't permanent cures and obesity results from a variety of factors with lifestyle and diet being major elements.
I was seriously obese for decades and about 9 years ago, hovering on the edge of becoming diabetic and other serious obesity-related health issues (high BP, IBS/GERDS, chronic apnea, etc), I decided I had to do something. GLP-1's weren't available then but none of the other typical approaches, including medically supervised diets worked more than a few months. Doing my own research, I discovered keto (this was before keto became big) and decided to try it. It was hard at first but also remarkably effective. I lost over 100 pounds in 8 months, becoming fit and seeing abs for the first time in my life. As I lost the weight, all the other health issues resolved too. But I knew if I returned to my previous diet and habits, I'd eventually grow obese again. Many people will take GLP-1s, lose weight but then stop and regain the weight because they didn't change their underlying behavior. Just like many people do with dieting, keto or any other intervention. But any intervention that works can be an invaluable for the few willing to understand, use it as a tool and do the work.
I stayed strict keto for 5 years. Long enough to train my body and mind how to be fit and healthy as normal (not a temporary diet). Then I started a rigorous process of gradually transitioning away from strict keto over a period of two years and that's also worked. I still eat a pretty low carb diet averaging less than 100g or less a day and will for life because there is no "Eat whatever junk you want and stay fit", at least for my metabolism. Reading that article, the criticisms of GLP-1s would also apply to keto or just "eat less, move more". If you stop the intervention, the system returns to state. However, for me keto helped me break an insidious pattern driven by habit, metabolism and blood sugar levels. I was then able to adopt new patterns. I suspect GLP-1s could help others in a similar way. Obviously, there is no magic drug that "cures" obesity by making you immune to bad habits and the physics of calories in/calories out.
It’s the perfect pharmaceutical miracle drug: a shot that cures the root cause for thousands of diseases (obesity) with a whole bunch of unexpected benefits (like reductions in substance abuse, fewer migraines), with mild symptoms and rare complications. But you’re stuck on it for life or else return to your pre GLP1 body.
The fact it spun of of research on Gila monsters is still crazy to me.
24 comments
[ 125 ms ] story [ 303 ms ] threadYou don't say ;-) I lost 50 lbs and have kept it off for the past year while maintaining great BP. But I'm under no illusions GLP-1 medications don't have dangers and cause problems for many. It should be handled on an individual basis like any serious medication.
That said, is someone losing a lot of weight then gaining half of it back worse than them just staying where they were? I don't know the answer to that one.
Compare that to something with no real off-ramp: testosterone replacement therapy. Once you're on TRT, you can permanently suppress your body's own testosterone production, and many men won't produce enough on their own afterward.
17.5% maintained 75+% of their weight loss. 25% maintained 50-75% of their weight loss. 23% maintained 25-50% of their weight loss. 24% maintained 0-25% of their weight loss.
I mean that's pretty good!
These symptoms will be familiar for anyone who has lost weight dieting and then returned to eating junk food.
So there appears to be an off-ramp, we just don't know what it is.
I think that it is quite unsurprising that without the drug a large amount of people revert to their previous behavior and with that will revert to their previous weight.
So weight loss was actually maintained for most people -- the hard part is finding a healthy daily lifestyle which can maintain the drastic effects of GLP1s.
This information isn't new -- weight regain has been studied before and I've written about it before:
https://glp1.guide/content/do-people-regain-all-the-weight-l...
The missing piece to this article is just how bad the alternative is -- never having the cardiovascular and metabolic benefits is clearly not the best strategy (and if simply changing patterns was so easy, people would have done it already).
GLP1s don't work for everyone but they're pretty close to miraculous in effect given the balance of positive and negative side effects. Making GLP1s cheaper & more tolerable then figuring out how to actually deal with the complex web of how to keep the weight off sustainably for most people seems like the right way forward here, not avoiding potentially life-saving medication because you may not be able to get off of it as fast as you want (if you can afford it).
BTW, there is already generic Liraglutide, and legal workarounds for getting compounded Semaglutide that already mean no one pays the $1000 that was in the zeitgeist a while ago. Even Lilly Direct and similar outfits from Novo sell for $500/month, with the $150/month pricing coming soon[0].
[0]: https://glp1guide.substack.com/p/negotiations-are-underway-f...
>stop taking weight loss drug
>regain weight
>there is no safe off-ramp for GLP-1
I guess taking weight loss drugs don't really teach healthy eating habits.
The struggle doesn't stop when you stop losing. My personal experience was that it takes about 2 years for the new 'normal' to kick in. (I lost 60lbs when I was in my early 20s and kept it off until today. The 'after' period was as taxing as the 'losing' period, but in a different way)
At that point only can you 'relax' a bit around your body's cravings for calories.
This has already been studied extensively:
https://pmc.ncbi.nlm.nih.gov/articles/PMC5764193/
It's not the worst thing in the world to be on a medication for a couple years rather than a few months, but long-term study of this class of drugs is certainly warranted and necessary.
My wife is back devouring cookies after being on mounjaro for 4 months. Thankfully she lost most weight all by herself so wasn’t totally reliant on the medication. But it’s crazy how noticeable the difference of one’s eating habits when on and off it.
Then, I stopped working out, and gained 15lbs. Exercise: no safe off-ramp for some.
Yes, you can loose weight without it, I did, I'm even in the healthy range now.
No, you don't have to, if you need medicine help, take it.
When I lost weight, I had my first real job that I liked so much, it didn't felt like one, 11 weeks of vacation per year, a nice enough apartment I couldn't be evicted of, great emotional support and advices and support from a doctor.
The only thing draining my willpower every day was the calorie restriction, and nothing else to worry about.
If you're in a similar spot I was, maybe trying a diet without glp-1 is better since we don't have any long term study on it yet, but if you're not: obesity will destroy your body more than any long term side effects can. Please take them if you can afford it.
The only thing I earned beside uncomfort and pain when I lost weight without drugs are internet points on hacker news, and the ability to say 'i did it' (also glp-1 didn't exist, so less long term health issues from obesity). Honestly if I had to redo it, I would take the drug despite a similar situation. Weight loss is hard, and not being able to do it without help is not an indictment on you or your character, but on your situation.
I suspect the manufacturers view this as a feature not a bug. :-) More seriously, I find the article's conclusions to be pretty much what I'd expect. Most medicines aren't permanent cures and obesity results from a variety of factors with lifestyle and diet being major elements.
I was seriously obese for decades and about 9 years ago, hovering on the edge of becoming diabetic and other serious obesity-related health issues (high BP, IBS/GERDS, chronic apnea, etc), I decided I had to do something. GLP-1's weren't available then but none of the other typical approaches, including medically supervised diets worked more than a few months. Doing my own research, I discovered keto (this was before keto became big) and decided to try it. It was hard at first but also remarkably effective. I lost over 100 pounds in 8 months, becoming fit and seeing abs for the first time in my life. As I lost the weight, all the other health issues resolved too. But I knew if I returned to my previous diet and habits, I'd eventually grow obese again. Many people will take GLP-1s, lose weight but then stop and regain the weight because they didn't change their underlying behavior. Just like many people do with dieting, keto or any other intervention. But any intervention that works can be an invaluable for the few willing to understand, use it as a tool and do the work.
I stayed strict keto for 5 years. Long enough to train my body and mind how to be fit and healthy as normal (not a temporary diet). Then I started a rigorous process of gradually transitioning away from strict keto over a period of two years and that's also worked. I still eat a pretty low carb diet averaging less than 100g or less a day and will for life because there is no "Eat whatever junk you want and stay fit", at least for my metabolism. Reading that article, the criticisms of GLP-1s would also apply to keto or just "eat less, move more". If you stop the intervention, the system returns to state. However, for me keto helped me break an insidious pattern driven by habit, metabolism and blood sugar levels. I was then able to adopt new patterns. I suspect GLP-1s could help others in a similar way. Obviously, there is no magic drug that "cures" obesity by making you immune to bad habits and the physics of calories in/calories out.
When the treatment is ceased, the benefits go away.
The fact it spun of of research on Gila monsters is still crazy to me.