4 ms·

There may not be a safe off-ramp for some taking GLP-1 drugs, study suggests

74 points by voxadam 11mo ago

petercooper 11mo ago
"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.
- quesera 11mo ago
  > losing a lot of weight then gaining half of it back The trick, of course, is to repeat the process as you asymptotically approach your goal. Zeno's paradox of mass.
Mistletoe 11mo ago
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.
- eps 11mo ago
  > take it for life That's literally the implication of these findings. But one can always hope for a miracle drug that you can take for a bit, then stop, and have its effects last. Now we know that Ozempic is not that drug.
  - RankingMember 11mo ago
    I think it would almost need to be some sort of genetic modifier, which may not be that far off.
- unethical_ban 11mo ago
  I imagine the idea for some is "if I can just get myself healthier, I can then stay motivated to maintain the healthier lifestyle required to stay skinny without the drugs"
- saurik 11mo ago
  > Why would someone think they would keep the weight off? If they could they would have before Ozempic. I think the intuition many people have--which I am not at all defending as correct, but it certainly isn't so obviously wrong that we should scoff at someone for thinking it works this way--is more like "if my weight was stable before I did this intervention, I just need to lose the weight and then my weight will once again be stable after it"; in this mental model, one would assume you only need lots of willpower to lose weight: after, you only will need as much willpower as you already know you have to not gain it back, as it isn't as if you are gaining weight currently.
  - Mistletoe 11mo ago
    Yes I can see that completely, but we see the data doesn’t support it. The issue was biological all along.
- rhines 11mo ago
  I could see it building habits that persist even when no longer using the drugs. They've found other things to fill their time instead of eating, and things which would previously trigger them to start eating now trigger them to do other things. There's of course a risk that when they stop the drugs that hunger will drive them to re-establish those habits, but now that they have new habits that fight that hunger they are in a much better position to resist it than they were when they'd initially established their eating patterns.
tyleo 11mo ago
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.
- gtirloni 11mo ago
  If you're on TRT, you are already not producing enough on your own.
  - tortilla 11mo ago
    Unless you went on when you weren't really low because the men's vitality clinic pushed you into a treatment protocol* * not me but I see it with men in my age range
    - PartiallyTyped 11mo ago
      I am a big fan of Dr Rohin Francis, and this landed on my youtube's front-page recently https://www.youtube.com/watch?v=FPsKTfFQFqc https://www.youtube.com/watch?v=FPsKTfFQFqc
    - Aurornis 11mo ago
      I’m getting downvoted in another comment for saying this, but it’s a growing problem. In some surveys of TRT patients up to 1/4 of them didn’t even have their testosterone levels measured before being prescribed TRT. The men’s health clinics are finding excuses to diagnose everyone who calls. The lifetime value of a monthly TRT customer is very high.
    - chimeracoder 11mo ago
      > Unless you went on when you weren't really low because the men's vitality clinic pushed you into a treatment protocol Saying that the men's vitality clinic "pushed you" into a treatment protocol is like saying that a fertility clinic pushed you into getting pregnant. Sure, it's a common outcome, but you had an idea of what you wanted out of it before you walked in the door.
elevation 11mo ago
> 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.
bryanlarsen 11mo ago
The headline doesn't seem to match the article? 20% of participants did keep the weight off and 40% kept half the weight off after stopping. So there appears to be an off-ramp, we just don't know what it is.
- NitpickLawyer 11mo ago
  > we just don't know what it is. calories_in < calories_out seems to be a pretty good formula.
  - falcor84 11mo ago
    It's almost the same as saying that the off-ramp for a cat to get off a tree is to apply a=g until h=0. It's technically correct, but I don't think it would help the cat to be aware of this.
  - orwin 11mo ago
    To a certain point yes, but also no. Depends on which fat you're talking about and which calories you are talking about (calories from carbs without fibers cost nothing to absorb, calories from fat cost more than half the energy they give you) (also if you have a good gut health, some calories are just never absorbed). Calorie restriction works up to a certain point, and weirdly the benefits aren't linear, and almost flat for visceral fat(i.e: if you're using 2.6 kcal a day and eating 2.4 kcal, you will loose roughly the same amount of visceral fat than if you only ate 1.8kcal, and slightly more 'external' fat (that one you shouldn't care much if you're only interested in health)). Calorie expenditure works linearly though, but it's hard to out-exercise your diet, and exercise while obese can be dangerous (my ankles still have to be reinforced despite me being under 24 BMI)
constantcrying 11mo ago
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.
- Argonaut998 11mo ago
  Indefinitely, not permanently
glp1guide 11mo ago
> 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: https://glp1.guide/content/do-people-regain-all-the-weight-lost-on-glp1-receptor-agonists/ 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-for-149 https://glp1guide.substack.com/p/negotiations-are-underway-f...
- axxto 11mo ago
  > 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.
  - apple4ever 11mo ago
    They still lost weight from their original amount right? That's the key. They may have come up from their lowest, but they still better off.
samlinnfer 11mo ago
>have unhealthy habits that causes weight gain >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.
pajamasam 11mo ago
For comparison, there also doesn't seem to be a "safe off-ramp" for obese patients from other weight loss interventions either: https://pmc.ncbi.nlm.nih.gov/articles/PMC4396554 https://pmc.ncbi.nlm.nih.gov/articles/PMC4396554
perelin 11mo ago
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.
- aishsh 11mo ago
  > Given the general health benefits that are being observed with GLP1-s the only reason to get off them is costs imo There’s also the perverse incentives wrt broader society. Enabling the average person to control their physical health is orders of magnitude better for society and orders of magnitude less profitable than the current trends. Maybe a setup where glp drugs are nationalized and only used to further understand why we have an obesity epidemic and eventually finance changes to combat it? Ideally the drug makers would do this without requiring government intervention, but I doubt they will.
  - perelin 11mo ago
    100% agree. But that also feels like the elephant in the room somehow. Most western pension systems are stretched to (or beyond) their limits already. I expect that having GLP1-s widely available will extend the life of a LOT of people even further. And then ... what? Im really surprised that nobody talks about that.
    - array_key_first 11mo ago
      We bring back smoking. Come on say it with me - smo-king! smo-king! smo-king!
  - SpicyLemonZest 11mo ago
    What don't we understand about the obesity epidemic? The story seems pretty clear to me at this point: * Almost everyone has access to a wide variety of delicious food, which we on average enjoy eating more of than is required to maintain a healthy weight. * We don't want the government to forcibly restrict people's food access. * Research consistently shows that voluntary portion control works occasionally in the short term and not at all in the long term. * Many people have proposed specific ingredients or nutrient classes that can be adjusted in a person's diet to resolve obesity, but none to date have checked out. In principle, I suppose, there could be some crazy diet hack we don't yet know about. But why should we expect that to be the case? To be honest, I think a lot of the existing discourse on this topic was just wishful thinking, because before GLP-1s the bottom line was not "some people need a pharmaceutical intervention" but "some people are just gonna be obese and there's nothing we can do to help them".
lkey 11mo ago
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. This has already been studied extensively: https://pmc.ncbi.nlm.nih.gov/articles/PMC5764193/ 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.
Argonaut998 11mo ago
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.
jitl 11mo ago
It’s the same as any other intervention to reduce weight. I worked out and ate better for a year and lost 35lbs. Then, I stopped working out, and gained 15lbs. Exercise: no safe off-ramp for some.
jtrn 11mo ago
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.
orwin 11mo ago
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.
- apple4ever 11mo ago
  Really really thoughtful reply, and a great counter point to the "just will it and you'll be fine!" arguments
mrandish 11mo ago
> "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.
ghostbrainalpha 11mo ago
By the same logic we could say that there is no safe off-ramp from any diet or exercise protocol. When the treatment is ceased, the benefits go away.
deleted 11mo ago
[deleted]
kawfey 11mo ago
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.
deleted 11mo ago
[deleted]

74 points by voxadam 11mo ago

"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.

quesera 11mo ago
> losing a lot of weight then gaining half of it back The trick, of course, is to repeat the process as you asymptotically approach your goal. Zeno's paradox of mass.

Mistletoe 11mo ago

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.

eps 11mo ago
> take it for life That's literally the implication of these findings. But one can always hope for a miracle drug that you can take for a bit, then stop, and have its effects last. Now we know that Ozempic is not that drug.
- RankingMember 11mo ago
  I think it would almost need to be some sort of genetic modifier, which may not be that far off.
unethical_ban 11mo ago
I imagine the idea for some is "if I can just get myself healthier, I can then stay motivated to maintain the healthier lifestyle required to stay skinny without the drugs"
saurik 11mo ago
> Why would someone think they would keep the weight off? If they could they would have before Ozempic. I think the intuition many people have--which I am not at all defending as correct, but it certainly isn't so obviously wrong that we should scoff at someone for thinking it works this way--is more like "if my weight was stable before I did this intervention, I just need to lose the weight and then my weight will once again be stable after it"; in this mental model, one would assume you only need lots of willpower to lose weight: after, you only will need as much willpower as you already know you have to not gain it back, as it isn't as if you are gaining weight currently.
- Mistletoe 11mo ago
  Yes I can see that completely, but we see the data doesn’t support it. The issue was biological all along.
rhines 11mo ago
I could see it building habits that persist even when no longer using the drugs. They've found other things to fill their time instead of eating, and things which would previously trigger them to start eating now trigger them to do other things. There's of course a risk that when they stop the drugs that hunger will drive them to re-establish those habits, but now that they have new habits that fight that hunger they are in a much better position to resist it than they were when they'd initially established their eating patterns.

tyleo 11mo ago

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.

gtirloni 11mo ago
If you're on TRT, you are already not producing enough on your own.
- tortilla 11mo ago
  Unless you went on when you weren't really low because the men's vitality clinic pushed you into a treatment protocol* * not me but I see it with men in my age range
  - PartiallyTyped 11mo ago
    I am a big fan of Dr Rohin Francis, and this landed on my youtube's front-page recently https://www.youtube.com/watch?v=FPsKTfFQFqc https://www.youtube.com/watch?v=FPsKTfFQFqc
  - Aurornis 11mo ago
    I’m getting downvoted in another comment for saying this, but it’s a growing problem. In some surveys of TRT patients up to 1/4 of them didn’t even have their testosterone levels measured before being prescribed TRT. The men’s health clinics are finding excuses to diagnose everyone who calls. The lifetime value of a monthly TRT customer is very high.
  - chimeracoder 11mo ago
    > Unless you went on when you weren't really low because the men's vitality clinic pushed you into a treatment protocol Saying that the men's vitality clinic "pushed you" into a treatment protocol is like saying that a fertility clinic pushed you into getting pregnant. Sure, it's a common outcome, but you had an idea of what you wanted out of it before you walked in the door.

elevation 11mo ago

> 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.

bryanlarsen 11mo ago

The headline doesn't seem to match the article? 20% of participants did keep the weight off and 40% kept half the weight off after stopping. So there appears to be an off-ramp, we just don't know what it is.

NitpickLawyer 11mo ago
> we just don't know what it is. calories_in < calories_out seems to be a pretty good formula.
- falcor84 11mo ago
  It's almost the same as saying that the off-ramp for a cat to get off a tree is to apply a=g until h=0. It's technically correct, but I don't think it would help the cat to be aware of this.
- orwin 11mo ago
  To a certain point yes, but also no. Depends on which fat you're talking about and which calories you are talking about (calories from carbs without fibers cost nothing to absorb, calories from fat cost more than half the energy they give you) (also if you have a good gut health, some calories are just never absorbed). Calorie restriction works up to a certain point, and weirdly the benefits aren't linear, and almost flat for visceral fat(i.e: if you're using 2.6 kcal a day and eating 2.4 kcal, you will loose roughly the same amount of visceral fat than if you only ate 1.8kcal, and slightly more 'external' fat (that one you shouldn't care much if you're only interested in health)). Calorie expenditure works linearly though, but it's hard to out-exercise your diet, and exercise while obese can be dangerous (my ankles still have to be reinforced despite me being under 24 BMI)

constantcrying 11mo ago

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.

Argonaut998 11mo ago
Indefinitely, not permanently

glp1guide 11mo ago

> 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: https://glp1.guide/content/do-people-regain-all-the-weight-lost-on-glp1-receptor-agonists/ 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-for-149 https://glp1guide.substack.com/p/negotiations-are-underway-f...

axxto 11mo ago
> 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.
- apple4ever 11mo ago
  They still lost weight from their original amount right? That's the key. They may have come up from their lowest, but they still better off.

samlinnfer 11mo ago

>have unhealthy habits that causes weight gain >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.

pajamasam 11mo ago

For comparison, there also doesn't seem to be a "safe off-ramp" for obese patients from other weight loss interventions either: https://pmc.ncbi.nlm.nih.gov/articles/PMC4396554 https://pmc.ncbi.nlm.nih.gov/articles/PMC4396554

perelin 11mo ago

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.

aishsh 11mo ago
> Given the general health benefits that are being observed with GLP1-s the only reason to get off them is costs imo There’s also the perverse incentives wrt broader society. Enabling the average person to control their physical health is orders of magnitude better for society and orders of magnitude less profitable than the current trends. Maybe a setup where glp drugs are nationalized and only used to further understand why we have an obesity epidemic and eventually finance changes to combat it? Ideally the drug makers would do this without requiring government intervention, but I doubt they will.
- perelin 11mo ago
  100% agree. But that also feels like the elephant in the room somehow. Most western pension systems are stretched to (or beyond) their limits already. I expect that having GLP1-s widely available will extend the life of a LOT of people even further. And then ... what? Im really surprised that nobody talks about that.
  - array_key_first 11mo ago
    We bring back smoking. Come on say it with me - smo-king! smo-king! smo-king!
- SpicyLemonZest 11mo ago
  What don't we understand about the obesity epidemic? The story seems pretty clear to me at this point: * Almost everyone has access to a wide variety of delicious food, which we on average enjoy eating more of than is required to maintain a healthy weight. * We don't want the government to forcibly restrict people's food access. * Research consistently shows that voluntary portion control works occasionally in the short term and not at all in the long term. * Many people have proposed specific ingredients or nutrient classes that can be adjusted in a person's diet to resolve obesity, but none to date have checked out. In principle, I suppose, there could be some crazy diet hack we don't yet know about. But why should we expect that to be the case? To be honest, I think a lot of the existing discourse on this topic was just wishful thinking, because before GLP-1s the bottom line was not "some people need a pharmaceutical intervention" but "some people are just gonna be obese and there's nothing we can do to help them".

lkey 11mo ago

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. This has already been studied extensively: https://pmc.ncbi.nlm.nih.gov/articles/PMC5764193/ 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.

Argonaut998 11mo ago

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.

jitl 11mo ago

It’s the same as any other intervention to reduce weight. I worked out and ate better for a year and lost 35lbs. Then, I stopped working out, and gained 15lbs. Exercise: no safe off-ramp for some.

jtrn 11mo ago

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.

orwin 11mo ago

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.

apple4ever 11mo ago
Really really thoughtful reply, and a great counter point to the "just will it and you'll be fine!" arguments

mrandish 11mo ago

> "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.

ghostbrainalpha 11mo ago

By the same logic we could say that there is no safe off-ramp from any diet or exercise protocol. When the treatment is ceased, the benefits go away.

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kawfey 11mo ago

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.

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