6 ms·

Discontinuation and reinitiation of dual-labeled GLP-1 receptor agonists

86 points by siquick 7mo ago

Study: https://pubmed.ncbi.nlm.nih.gov/39888616/ https://pubmed.ncbi.nlm.nih.gov/39888616/

Robotbeat 7mo ago
Kind of makes sense that stopping taking a drug that reduces heart attack and stroke risk leads to a return to the higher risk of before.
- ErroneousBosh 7mo ago
  It doesn't reduce heart attack and stroke. It reduces appetite, kind of, and gives you a sore stomach while making you shit yourself inside out. All this can, with care, help contribute to weight loss. Weight loss can reduce heart attack and stroke, but GLP-1 does not. You could also reduce heart attack and stroke risks by not eating crap and going for a walk every so often.
  - malfist 7mo ago
    Your comment is all kinds of wrong. A) it does have cardio protective effects. It does reduce your appetite, and for most people have very few side effects. If you get nausea you're titrating up too fast. Most people, because it slows gastric emptying, it doesn't make them shit themselves "inside and out". GLP1s are a decent option for treating ibs-d or bile acid issues and is better tolerated than your bile acid sequesterants. > You could also reduce heart attack and stroke risks by not eating crap and going for a walk every so often. This victim blaming advice has been given for decades and obesity rates have been climbing for decades. Only glp-1s have reduced that.
  - cthalupa 7mo ago
    We see risk reduction for heart attack and stroke for people on GLP-1s even without weight loss, which belies the idea that the protection only comes from losing weight. Edit: In fact, from the study - BMI went from 35.86 (Continued) to 34.57 (Discontinued) to 35.48 (Interrupted), Heart failure percentage was 11.57% for continued use, 12.73% for discontinued, 11.92% for interrupted NICM went 3.10% for continued, 3.36% for discontinued, 3.31% for interrupted BMI was higher for the continuing users and they still had lower heart failure and NICM rates than the discontinued and interrupted groups. (Also a bunch of other things including stroke and heart attack but I didn't want to write all of these out)
    - ErroneousBosh 7mo ago
      Have you got a link to the study those figures are actually from? I'm not saying their wrong but I would like to read and understand them for myself before I change my mind. > BMI went from 35.86 (Continued) to 34.57 (Discontinued) to 35.48 (Interrupted), So, what, was 35.86 the BMI at the start, 34.57 the BMI when they stopped taking the drug, and 35.48 after some interval? For someone of a fairly average height, say 1.86 metres (that's a little under how tall I am) a BMI of 35.86 would be 124kg which is ridiculously fat and 34.57 would be around 119.6kg so you're looking at a loss of around 4.5kg or so. That's a good shit and a haircut, in the grand scheme of things. It's fairly normal for someone's weight to fluctuate by a kilo up or down (a range of 2kg over normal) and not utterly off the map for a range of four kilos on a day-to-day basis, especially in obese people. That's why you're not supposed to keep weighing yourself and obsessing over the weight.
  - rootusrootus 7mo ago
    What is it about GLP1s that bring out the kooks who suddenly think diet and exercise are the only valid medical treatment? Is it a moral issue?
    - cthalupa 7mo ago
      As best as I can tell, people are very attached to having achieved their body weight through whatever means they have determined are valid and derive self value from it, and believe that GLP-1s are cheating to achieve a result they worked harder for.
    - sublinear 7mo ago
      Unless we're talking about emergency care, most pharmaceuticals are completely unnecessary and carry serious risks. There's not a single qualified doctor out there that would promote drugs before preventative measures.
      - cthalupa 7mo ago
        Pretty much every adult fat person has attempted diet and exercise to resolve their weight issue. Saying they should try this first at this point in the game is like having your support case escalated 5 times already and them saying "have you tried turning it off and on again"
        ErroneousBosh 7mo ago
        > Pretty much every adult fat person has attempted diet and exercise to resolve their weight issue. If it's not working for you, it may be because you haven't sorted the "diet" bit. Are you eating "low fat" or "low calorie" things? Because those are not food and they will make you fat. Eat food, just a bit less of it than you do now.
        cthalupa 7mo ago
        Obviously the calories in are greater than the calories out if the diet doesn't work. That's not the point. The point is the vast majority of overweight and obese people try to diet and do not succeed in it.
  - shlant 7mo ago
    > You could also reduce heart attack and stroke risks by not eating crap and going for a walk every so often. Oh wow it's so simple! why has nobody thought of this before??
    - ErroneousBosh 7mo ago
      You've been being told this your whole life. You still think mass-marketed "low fat" foods are good for you. You still think you can pop a pill to make your problems go away.
TaupeRanger 7mo ago
Kind of a useless analysis if it doesn't compare the risk after stopping GLP-1s to the risk of NEVER taking GLP-1s in the first place. We probably don't know the numbers yet, but one can easily envision a scenario like: risk of CE without GLP-1 weight loss: 20%. Risk after taking GLP-1s for 2 years: 10%. Risk after stopping GLP-1s: 12%. "Your heart attack chance goes up 20% after stopping GLP-1s!!!"
- gpt5 7mo ago
  Especially since every GLP-1 study shows almost complete regain to original weight after stopping. It’s like stopping a blood pressure medicine and then being surprised that people have more heart attacks afterwards.
  - cthalupa 7mo ago
    The discontinued and paused groups in the actual study had lower BMI than the continuing groups - so it seems like this is at least partially independent of any weight regain. Which makes sense since we have strong evidence for the GLP-1s providing significant protective benefit even without weight loss.
  - watermelon0 7mo ago
    There is a recent one, which shows that the weight was generally stable after 1 year of discontinuation of GLP-1. > In this cohort study of adults with overweight or obesity who initiated treatment with injectable semaglutide or tirzepatide and discontinued the index medication between 3 and 12 months after initiation, 19.6% restarted the index medication and 35.2% received an alternative treatment in the year after initial treatment discontinuation. The average weight change 1 year after index medication discontinuation was relatively small; however, there was considerable individual-level variability. https://dom-pubs.pericles-prod.literatumonline.com/doi/10.1111/dom.70660 https://dom-pubs.pericles-prod.literatumonline.com/doi/10.11...
    - gpt5 7mo ago
      Thanks for sharing. Note that the data quality from this study is quite low because 54.8% of the cohort eventually restarted their medication or transitioned to an alternative therapy (mostly a different weight loss medication). I don't know why a study that focuses on discontinuation didn't split the groups that restarted or transitioned against the group that actually just stopped.
rayiner 7mo ago
This is a very odd phrasing that makes it seem like heart attack and stroke risk are higher for those who stop taking the drug than those who never took the drug. Moreover, the effect of restarting taking the drug seems attributable to the study design. Those who took a break had higher risk at the end of the study than those who don’t. But those who took a break took the drug for less total time than those who took it for the entire study. You could characterize these same facts in the opposite way. GLP-1s don’t permanently change your body. They provide benefits while taking them but quickly clear out of your system when you stop taking them. Arguably, that’s a good thing in a drug.
- IAmGraydon 7mo ago
  >This is a very odd phrasing that makes it seem like heart attack and stroke risk are higher for those who stop taking the drug than those who never took the drug. That does appear to be the case, according to the study.
  - kube-system 7mo ago
    The conclusion of the study says: > This study showed that discontinuing and interrupting GLP-1RA treatment could erode and might reverse the cardiovascular benefits of the drug in a duration dependent manner, increasing the risk of cardiovascular events. emphasis mine
    - conception 7mo ago
      Could.
    - r-johnv 7mo ago
      Reverse the benefits != increase the net risk It took a while going through the data in the results section to see this.
  - post-it 7mo ago
    It certainly does not. To make that claim, the study would need a control group of people who had never taken the drug. They didn't have that: > Participants Veterans Affairs users with type 2 diabetes who started treatment with GLP-1RAs (n=132 551) or sulfonylureas (n=201 136), followed up for three years. Veterans Affairs users were defined as having at least two visits to Veterans Affairs and having used the Veterans Affairs outpatient pharmacy within a year before receiving treatment with GLP-1RAs or sulfonylureas.
ldayley 7mo ago
How much of this could attributed to simply having less artificial hormonal support for not overeating after discontinuing treatment, and falling back into old habits? I’d love to see more research focused on these mechanisms.
46493168 7mo ago
In veterans with T2 diabetes: > To find out what happens when people stop taking GLP-1s, Al-Aly’s team of researchers tracked the health of more than 333,000 United States veterans with type 2 diabetes for three years.
- actuallyalys 7mo ago
  The same thing happened when the same researcher did studies on Covid using similar datasets. There’s likely some generalizability but part of the reason the absolute risk is so high is because VA patients are a group already at high risk. It’s partly a failure of science journalism this caveat gets missed but seems like it is also one Al-Aly is happy to allow.
bethekidyouwant 7mo ago
Studies get worse every year.
- jimbokun 7mo ago
  Or articles that try to convey the content of studies have always been poor and continue to be poor.
jryio 7mo ago
We finally found the first morbidity signal of GLP-1s (or lack thereof). These are life changing drugs, but like plastic we'll see their effects in force within this generation: > The longer time spent off GLP-1s, the greater the risk of major cardiovascular events—up to 22 percent for those who abstained for two years.
- stavros 7mo ago
  Doesn't it make sense that, if you were taking a drug that reduces morbidity, you'll get increased morbidity if you stop it?
  - jryio 7mo ago
    Not if having a heart attack within 1 year at a higher rate is an co-morbidity factor when the primary treatment was for obesity or diabetes (not stating that obesity and heart disease are not positively correlated). To use a dense analogy: if I stopped brushing my teeth I would not expect to die of gum disease.
    - malfist 7mo ago
      I don't think you read the study. The people returned to their pre treatment risk profile after ceasing treatment
- cthalupa 7mo ago
  You are misunderstanding the study (largely because the article heavily misrepresents it, would be my guess) They do not see an increase against their pre-GLP1 baseline risk - they see a reversal of the cardioprotective benefits the drug provided while they were on it.
- TaupeRanger 7mo ago
  You failed to understand the results of the study and quoted a passage that does not in any way support your assertion.
bradleyy 7mo ago
The actual study states in the summary that it's the cardiac protective improvement that reverses, not that you're worse off for having taken a GLP-1. So yeah, when you stop taking something that protects your heart and kidneys, it stops protecting... your heart and kidneys. There's an increasing body of work that indicates that long-term GLP use (initially higher doses for weight loss, then tapering down) retains the cardiac and kidney benefits and can actually lead to additional weight loss.
- 46493168 7mo ago
  > So yeah, when you stop taking something that protects your heart and kidneys, it stops protecting... your heart and kidneys. This is not at all obvious and still requires further study. Do the drugs themselves have heart- and kidney- protective effects, or are the heart and kidneys protected by maintaining a lower weight, or lower resting blood glucose, or lower inflammation, all of which are effects of the drug?
nisegami 7mo ago
This makes it even more fantastic that the supply of GLP1s from my country's only legal importer is spotty and I've been suddenly cut off twice already
- rootusrootus 7mo ago
  One benefit of going gray is that you can stock up. If I could not get any more, it would be a number of years before I ran out.
deleted 7mo ago
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0x3f 7mo ago
Others have addressed the clickbait nature of the title I'm just surprised the food industry or whoever is willing to fund FUD content that ostensibly has such an indirect effect on their bottom line. Although I guess they spend a ton on ads which are also of dubious value, so maybe it's to be expected.
Aboutplants 7mo ago
Also News I guess - People who pick up smoking again after a period of cessation, regain all negative effects of smoking that they previously experienced during that past smoking periods, eliminating the positive effects of the smoking cessation.
Aboutplants 7mo ago
The most capitalistic drug ever! Take the drug forever and lose weight but stop taking it and you’ll die.
- devin 7mo ago
  That isn’t what this says at all.
  - mh- 7mo ago
    (off-topic, but since the thread already is..) HN felt like one of the last places on the internet I could have good-faith conversations with intelligent people who would form thoughtful, on-topic replies. And now it feels like the user base here has shifted enough that the voting system no longer consistently elevates the interesting comments, but the comments that reinforce people's worldviews.
    - TaupeRanger 7mo ago
      What do you mean? All of the comments that misunderstand the study are downvoted from what I see.
    - arjie 7mo ago
      Everyone feels Eternal September sooner or later. I recommend blocking users on this site. Having hit about 800 or so blocks I find that the conversation quality has skyrocketed. You still get one or two low quality users on a thread like this (I hadn’t blocked this guy) but the truth is that it’s usually a few people. Any time a user gives me a flash of annoyance with a nonsensical comment that’s the last time I see them. This isn’t a native feature but Claude will implement it for you in a really short amount of time. If you want a feature set to copy or a list of users to seed, you can just copy mine (in profile).
      - mh- 7mo ago
        Yeah, unfortunate that it's come to that, but I think you're right. I started to write a comment about having some (additional) ideas for a Chrome extension, clicked your profile, watched the YouTube video. Fantastic. I think it already does everything I wanted. Thank you for making and open sourcing this!
Teknoman117 7mo ago
I’m always kind of envious of the people who were able to lose weight on GLP-1 drugs. I lost a bunch of weight a few years ago, and still need to lose a lot more (430 lb -> 330, goal 240), but I fell out of the good habits for, well, no good reasons… Decided to try Ozempic and was on it for about 6 months. Didn’t do a single thing for my appetite unfortunately, even on the max dose. Sample size of one here, but if you’ve got mental health struggles that feed into your eating patterns, GLP-1s might not help with your weight problems.
- bradleyy 7mo ago
  Hey, I can identify. Sending good thoughts your way.
- cthalupa 7mo ago
  That's unfortunate! It might be worth checking out Tirzepatide or Retatrutide once it is released. The GIP and Glucagon receptors might be better targets for you, even if the GLP-1 receptor seems to not help.
- pitched 7mo ago
  I really had thought (with no research) the correlation between mental health and glp1 effectiveness went the other way around. Thank you for this check-your-biases moment, you probably just saved me a ton of embarrassment down the line, if these drugs ever enter my life.
  - phil21 7mo ago
    I don’t think there is remotely enough data on the subject to make any confident statements either way yet. I think the only very confident thing I can say after watching and helping dozens of folks get started on these drugs is that everyone’s biology is vastly different. I have friends who have lost close to a hundred pounds on the starting doses of their chosen GLP-1. I have other friends who barely lost anything after a year at max dose. Some of these people in both groups are highly motivated to lose weight and some are simply taking the drug as a magic fix and expending zero other effort into changing their lives. Some have very difficult mental issues and relationships with food, some have very few hangups on the subject. I have never been able to predict with high confidence how any particular person is going to react to taking them. By and large the results are close to magical for the majority of folks, and there may be some correlation with folks who combine the drug with other lifestyle changes - but those are just general averages I see and certainly not scientific.
mullingitover 7mo ago
I mostly feel bad for job losses due to AI, but I won't shed a tear for journalists who make a living spreading misinformation about the results of research. > They found that the risk of heart attack and stroke jumped in those that paused GLP-1 treatments for as little as six months, compared to those who continued taking the medication. (Emphasis mine) The 'jumped' would more correctly say 'tended to revert to baseline' if you just had a basic LLM summarize this study for you...but then that wouldn't drive clicks and shares on your article.
amazingamazing 7mo ago
Honestly don’t understand it. Feels like a lack of discipline. I was 250. Plugged in a bunch of numbers into an app and it gave me a calorie count per day. I brought a scale with me everywhere, used ChatGPT to guesstimate calories, I added 50% for good measure. A year later I’m 175. You can’t do this even with drugs you’re gonna get fat anyway. I’m most curious about someone like me vs someone who lost the same amount on glp1 with respect to these stats
- rootusrootus 7mo ago
  We know that GLP1s have benefits that are disproportionate with just weight loss, so someone who is otherwise like you in terms of weight loss would probably have better cardiovascular markers. Probably the biggest difference, though, is that an average "you" will be back at original weight, plus a little, in about a year, while the average GLP1 user will (assuming they keep taking it) be the same weight, or even a bit lighter.
- renewiltord 7mo ago
  Everything is discipline. If you just always do the thing you’re supposed to you will win at life. People can’t always do the thing they’re supposed to so they supplement with drugs that help them do it: caffeine, amphetamine, SSRIs, GLP-1RAs and related drugs. In fact, everything is discipline. If you were disciplined enough to always put the basketball in the net from anywhere on the court you’d be Steph Curry. The thing is most people don’t have that kind of discipline. Someone runs up to them and puts their hand up in the air? They shoot wide or balk. Curry shoots true. Discipline. Just always do the right thing and never do the wrong thing and you’ll be fine at literally everything.
  - amazingamazing 7mo ago
    Some things require talent like your examples, weight loss does not imho. The disparities in obesity and culture within country says it all.
    - cthalupa 7mo ago
deleted 7mo ago
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storus 7mo ago
Isn't GLP-1 creating a "feel-good" starvation? Patching the receptors telling the brain one is not hungry and then just letting the body starve happily, leading to significant muscle loss and aged face? Contrary to e.g. water fast where the body switches to 100% ketosis that can run as long as there is any fat in the body and one supplements electrolytes (Mg/K/P/HCO3) and vitamins (predominantly B1/B2/B3), leading to a much more healthy appearance?
- mrtesthah 7mo ago
  There is nothing inherent in your description that would support your implied claim about facial aging.
  - storus 7mo ago
    "Emerging research suggests GLP‑1 receptors are present on adipocytes and fibroblasts. Some animal studies indicate that GLP‑1 agonism may promote lipolysis in subcutaneous fat more aggressively than in visceral fat, leading to disproportionate loss of facial fat. It also may affect collagen synthesis or skin architecture, though human data are still evolving."
- rootusrootus 7mo ago
  GLP1s do not themselves cause any worse muscle loss than you would experience if you lost the weight by watching calories the old fashioned way. "Ozempic face" is almost certainly an artifact of people who spent their life significantly overweight having somewhat looser skin than they would if they had maintained a low weight throughout their life. Also, not everyone gets the face effect, not by a long shot.
  - gedy 7mo ago
    Yeah exactly, what people call Ozempic Face is often just wrinkles. I look a bit older now that I lost 40 lbs, but much healthier shape. Fat does fill in your face some
    - deleted 7mo ago
r-johnv 7mo ago
This is the study that the article references. (The linked one on the post is an older study) https://bmjmedicine.bmj.com/content/5/1/e002150 https://bmjmedicine.bmj.com/content/5/1/e002150
jeremie_strand 7mo ago
[flagged]
camillomiller 7mo ago
We built a world where food is so processed and toxic that it makes you easily fat, but instead of fixing that we invented a drug that makes you eat less. Why not invent a drug that makes you less thirsty for those whose water is contaminated by fracking?
liv_intel 6mo ago
[dead]

86 points by siquick 7mo ago

Study: https://pubmed.ncbi.nlm.nih.gov/39888616/ https://pubmed.ncbi.nlm.nih.gov/39888616/

Kind of makes sense that stopping taking a drug that reduces heart attack and stroke risk leads to a return to the higher risk of before.

ErroneousBosh 7mo ago
It doesn't reduce heart attack and stroke. It reduces appetite, kind of, and gives you a sore stomach while making you shit yourself inside out. All this can, with care, help contribute to weight loss. Weight loss can reduce heart attack and stroke, but GLP-1 does not. You could also reduce heart attack and stroke risks by not eating crap and going for a walk every so often.
- malfist 7mo ago
  Your comment is all kinds of wrong. A) it does have cardio protective effects. It does reduce your appetite, and for most people have very few side effects. If you get nausea you're titrating up too fast. Most people, because it slows gastric emptying, it doesn't make them shit themselves "inside and out". GLP1s are a decent option for treating ibs-d or bile acid issues and is better tolerated than your bile acid sequesterants. > You could also reduce heart attack and stroke risks by not eating crap and going for a walk every so often. This victim blaming advice has been given for decades and obesity rates have been climbing for decades. Only glp-1s have reduced that.
- cthalupa 7mo ago
  We see risk reduction for heart attack and stroke for people on GLP-1s even without weight loss, which belies the idea that the protection only comes from losing weight. Edit: In fact, from the study - BMI went from 35.86 (Continued) to 34.57 (Discontinued) to 35.48 (Interrupted), Heart failure percentage was 11.57% for continued use, 12.73% for discontinued, 11.92% for interrupted NICM went 3.10% for continued, 3.36% for discontinued, 3.31% for interrupted BMI was higher for the continuing users and they still had lower heart failure and NICM rates than the discontinued and interrupted groups. (Also a bunch of other things including stroke and heart attack but I didn't want to write all of these out)
  - ErroneousBosh 7mo ago
    Have you got a link to the study those figures are actually from? I'm not saying their wrong but I would like to read and understand them for myself before I change my mind. > BMI went from 35.86 (Continued) to 34.57 (Discontinued) to 35.48 (Interrupted), So, what, was 35.86 the BMI at the start, 34.57 the BMI when they stopped taking the drug, and 35.48 after some interval? For someone of a fairly average height, say 1.86 metres (that's a little under how tall I am) a BMI of 35.86 would be 124kg which is ridiculously fat and 34.57 would be around 119.6kg so you're looking at a loss of around 4.5kg or so. That's a good shit and a haircut, in the grand scheme of things. It's fairly normal for someone's weight to fluctuate by a kilo up or down (a range of 2kg over normal) and not utterly off the map for a range of four kilos on a day-to-day basis, especially in obese people. That's why you're not supposed to keep weighing yourself and obsessing over the weight.
- rootusrootus 7mo ago
  What is it about GLP1s that bring out the kooks who suddenly think diet and exercise are the only valid medical treatment? Is it a moral issue?
  - cthalupa 7mo ago
    As best as I can tell, people are very attached to having achieved their body weight through whatever means they have determined are valid and derive self value from it, and believe that GLP-1s are cheating to achieve a result they worked harder for.
  - sublinear 7mo ago
    Unless we're talking about emergency care, most pharmaceuticals are completely unnecessary and carry serious risks. There's not a single qualified doctor out there that would promote drugs before preventative measures.
    - cthalupa 7mo ago
      Pretty much every adult fat person has attempted diet and exercise to resolve their weight issue. Saying they should try this first at this point in the game is like having your support case escalated 5 times already and them saying "have you tried turning it off and on again"
      - ErroneousBosh 7mo ago
        > Pretty much every adult fat person has attempted diet and exercise to resolve their weight issue. If it's not working for you, it may be because you haven't sorted the "diet" bit. Are you eating "low fat" or "low calorie" things? Because those are not food and they will make you fat. Eat food, just a bit less of it than you do now.
        cthalupa 7mo ago
        Obviously the calories in are greater than the calories out if the diet doesn't work. That's not the point. The point is the vast majority of overweight and obese people try to diet and do not succeed in it.
- shlant 7mo ago
  > You could also reduce heart attack and stroke risks by not eating crap and going for a walk every so often. Oh wow it's so simple! why has nobody thought of this before??
  - ErroneousBosh 7mo ago
    You've been being told this your whole life. You still think mass-marketed "low fat" foods are good for you. You still think you can pop a pill to make your problems go away.

TaupeRanger 7mo ago

Kind of a useless analysis if it doesn't compare the risk after stopping GLP-1s to the risk of NEVER taking GLP-1s in the first place. We probably don't know the numbers yet, but one can easily envision a scenario like: risk of CE without GLP-1 weight loss: 20%. Risk after taking GLP-1s for 2 years: 10%. Risk after stopping GLP-1s: 12%. "Your heart attack chance goes up 20% after stopping GLP-1s!!!"

gpt5 7mo ago
Especially since every GLP-1 study shows almost complete regain to original weight after stopping. It’s like stopping a blood pressure medicine and then being surprised that people have more heart attacks afterwards.
- cthalupa 7mo ago
  The discontinued and paused groups in the actual study had lower BMI than the continuing groups - so it seems like this is at least partially independent of any weight regain. Which makes sense since we have strong evidence for the GLP-1s providing significant protective benefit even without weight loss.
- watermelon0 7mo ago
  There is a recent one, which shows that the weight was generally stable after 1 year of discontinuation of GLP-1. > In this cohort study of adults with overweight or obesity who initiated treatment with injectable semaglutide or tirzepatide and discontinued the index medication between 3 and 12 months after initiation, 19.6% restarted the index medication and 35.2% received an alternative treatment in the year after initial treatment discontinuation. The average weight change 1 year after index medication discontinuation was relatively small; however, there was considerable individual-level variability. https://dom-pubs.pericles-prod.literatumonline.com/doi/10.1111/dom.70660 https://dom-pubs.pericles-prod.literatumonline.com/doi/10.11...
  - gpt5 7mo ago
    Thanks for sharing. Note that the data quality from this study is quite low because 54.8% of the cohort eventually restarted their medication or transitioned to an alternative therapy (mostly a different weight loss medication). I don't know why a study that focuses on discontinuation didn't split the groups that restarted or transitioned against the group that actually just stopped.

rayiner 7mo ago

This is a very odd phrasing that makes it seem like heart attack and stroke risk are higher for those who stop taking the drug than those who never took the drug. Moreover, the effect of restarting taking the drug seems attributable to the study design. Those who took a break had higher risk at the end of the study than those who don’t. But those who took a break took the drug for less total time than those who took it for the entire study. You could characterize these same facts in the opposite way. GLP-1s don’t permanently change your body. They provide benefits while taking them but quickly clear out of your system when you stop taking them. Arguably, that’s a good thing in a drug.

IAmGraydon 7mo ago
>This is a very odd phrasing that makes it seem like heart attack and stroke risk are higher for those who stop taking the drug than those who never took the drug. That does appear to be the case, according to the study.
- kube-system 7mo ago
  The conclusion of the study says: > This study showed that discontinuing and interrupting GLP-1RA treatment could erode and might reverse the cardiovascular benefits of the drug in a duration dependent manner, increasing the risk of cardiovascular events. emphasis mine
  - conception 7mo ago
    Could.
  - r-johnv 7mo ago
    Reverse the benefits != increase the net risk It took a while going through the data in the results section to see this.
- post-it 7mo ago
  It certainly does not. To make that claim, the study would need a control group of people who had never taken the drug. They didn't have that: > Participants Veterans Affairs users with type 2 diabetes who started treatment with GLP-1RAs (n=132 551) or sulfonylureas (n=201 136), followed up for three years. Veterans Affairs users were defined as having at least two visits to Veterans Affairs and having used the Veterans Affairs outpatient pharmacy within a year before receiving treatment with GLP-1RAs or sulfonylureas.

ldayley 7mo ago

How much of this could attributed to simply having less artificial hormonal support for not overeating after discontinuing treatment, and falling back into old habits? I’d love to see more research focused on these mechanisms.

46493168 7mo ago

In veterans with T2 diabetes: > To find out what happens when people stop taking GLP-1s, Al-Aly’s team of researchers tracked the health of more than 333,000 United States veterans with type 2 diabetes for three years.

actuallyalys 7mo ago
The same thing happened when the same researcher did studies on Covid using similar datasets. There’s likely some generalizability but part of the reason the absolute risk is so high is because VA patients are a group already at high risk. It’s partly a failure of science journalism this caveat gets missed but seems like it is also one Al-Aly is happy to allow.

bethekidyouwant 7mo ago

Studies get worse every year.

jimbokun 7mo ago
Or articles that try to convey the content of studies have always been poor and continue to be poor.

jryio 7mo ago

We finally found the first morbidity signal of GLP-1s (or lack thereof). These are life changing drugs, but like plastic we'll see their effects in force within this generation: > The longer time spent off GLP-1s, the greater the risk of major cardiovascular events—up to 22 percent for those who abstained for two years.

stavros 7mo ago
Doesn't it make sense that, if you were taking a drug that reduces morbidity, you'll get increased morbidity if you stop it?
- jryio 7mo ago
  Not if having a heart attack within 1 year at a higher rate is an co-morbidity factor when the primary treatment was for obesity or diabetes (not stating that obesity and heart disease are not positively correlated). To use a dense analogy: if I stopped brushing my teeth I would not expect to die of gum disease.
  - malfist 7mo ago
    I don't think you read the study. The people returned to their pre treatment risk profile after ceasing treatment
cthalupa 7mo ago
You are misunderstanding the study (largely because the article heavily misrepresents it, would be my guess) They do not see an increase against their pre-GLP1 baseline risk - they see a reversal of the cardioprotective benefits the drug provided while they were on it.
TaupeRanger 7mo ago
You failed to understand the results of the study and quoted a passage that does not in any way support your assertion.

bradleyy 7mo ago

The actual study states in the summary that it's the cardiac protective improvement that reverses, not that you're worse off for having taken a GLP-1. So yeah, when you stop taking something that protects your heart and kidneys, it stops protecting... your heart and kidneys. There's an increasing body of work that indicates that long-term GLP use (initially higher doses for weight loss, then tapering down) retains the cardiac and kidney benefits and can actually lead to additional weight loss.

46493168 7mo ago
> So yeah, when you stop taking something that protects your heart and kidneys, it stops protecting... your heart and kidneys. This is not at all obvious and still requires further study. Do the drugs themselves have heart- and kidney- protective effects, or are the heart and kidneys protected by maintaining a lower weight, or lower resting blood glucose, or lower inflammation, all of which are effects of the drug?

nisegami 7mo ago

This makes it even more fantastic that the supply of GLP1s from my country's only legal importer is spotty and I've been suddenly cut off twice already

rootusrootus 7mo ago
One benefit of going gray is that you can stock up. If I could not get any more, it would be a number of years before I ran out.

deleted 7mo ago

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0x3f 7mo ago

Others have addressed the clickbait nature of the title I'm just surprised the food industry or whoever is willing to fund FUD content that ostensibly has such an indirect effect on their bottom line. Although I guess they spend a ton on ads which are also of dubious value, so maybe it's to be expected.

Aboutplants 7mo ago

Also News I guess - People who pick up smoking again after a period of cessation, regain all negative effects of smoking that they previously experienced during that past smoking periods, eliminating the positive effects of the smoking cessation.

Aboutplants 7mo ago

The most capitalistic drug ever! Take the drug forever and lose weight but stop taking it and you’ll die.

devin 7mo ago
That isn’t what this says at all.
- mh- 7mo ago
  (off-topic, but since the thread already is..) HN felt like one of the last places on the internet I could have good-faith conversations with intelligent people who would form thoughtful, on-topic replies. And now it feels like the user base here has shifted enough that the voting system no longer consistently elevates the interesting comments, but the comments that reinforce people's worldviews.
  - TaupeRanger 7mo ago
    What do you mean? All of the comments that misunderstand the study are downvoted from what I see.
  - arjie 7mo ago
    Everyone feels Eternal September sooner or later. I recommend blocking users on this site. Having hit about 800 or so blocks I find that the conversation quality has skyrocketed. You still get one or two low quality users on a thread like this (I hadn’t blocked this guy) but the truth is that it’s usually a few people. Any time a user gives me a flash of annoyance with a nonsensical comment that’s the last time I see them. This isn’t a native feature but Claude will implement it for you in a really short amount of time. If you want a feature set to copy or a list of users to seed, you can just copy mine (in profile).
    - mh- 7mo ago
      Yeah, unfortunate that it's come to that, but I think you're right. I started to write a comment about having some (additional) ideas for a Chrome extension, clicked your profile, watched the YouTube video. Fantastic. I think it already does everything I wanted. Thank you for making and open sourcing this!

Teknoman117 7mo ago

I’m always kind of envious of the people who were able to lose weight on GLP-1 drugs. I lost a bunch of weight a few years ago, and still need to lose a lot more (430 lb -> 330, goal 240), but I fell out of the good habits for, well, no good reasons… Decided to try Ozempic and was on it for about 6 months. Didn’t do a single thing for my appetite unfortunately, even on the max dose. Sample size of one here, but if you’ve got mental health struggles that feed into your eating patterns, GLP-1s might not help with your weight problems.

bradleyy 7mo ago
Hey, I can identify. Sending good thoughts your way.
cthalupa 7mo ago
That's unfortunate! It might be worth checking out Tirzepatide or Retatrutide once it is released. The GIP and Glucagon receptors might be better targets for you, even if the GLP-1 receptor seems to not help.
pitched 7mo ago
I really had thought (with no research) the correlation between mental health and glp1 effectiveness went the other way around. Thank you for this check-your-biases moment, you probably just saved me a ton of embarrassment down the line, if these drugs ever enter my life.
- phil21 7mo ago
  I don’t think there is remotely enough data on the subject to make any confident statements either way yet. I think the only very confident thing I can say after watching and helping dozens of folks get started on these drugs is that everyone’s biology is vastly different. I have friends who have lost close to a hundred pounds on the starting doses of their chosen GLP-1. I have other friends who barely lost anything after a year at max dose. Some of these people in both groups are highly motivated to lose weight and some are simply taking the drug as a magic fix and expending zero other effort into changing their lives. Some have very difficult mental issues and relationships with food, some have very few hangups on the subject. I have never been able to predict with high confidence how any particular person is going to react to taking them. By and large the results are close to magical for the majority of folks, and there may be some correlation with folks who combine the drug with other lifestyle changes - but those are just general averages I see and certainly not scientific.

mullingitover 7mo ago

I mostly feel bad for job losses due to AI, but I won't shed a tear for journalists who make a living spreading misinformation about the results of research. > They found that the risk of heart attack and stroke jumped in those that paused GLP-1 treatments for as little as six months, compared to those who continued taking the medication. (Emphasis mine) The 'jumped' would more correctly say 'tended to revert to baseline' if you just had a basic LLM summarize this study for you...but then that wouldn't drive clicks and shares on your article.

amazingamazing 7mo ago

Honestly don’t understand it. Feels like a lack of discipline. I was 250. Plugged in a bunch of numbers into an app and it gave me a calorie count per day. I brought a scale with me everywhere, used ChatGPT to guesstimate calories, I added 50% for good measure. A year later I’m 175. You can’t do this even with drugs you’re gonna get fat anyway. I’m most curious about someone like me vs someone who lost the same amount on glp1 with respect to these stats

rootusrootus 7mo ago
We know that GLP1s have benefits that are disproportionate with just weight loss, so someone who is otherwise like you in terms of weight loss would probably have better cardiovascular markers. Probably the biggest difference, though, is that an average "you" will be back at original weight, plus a little, in about a year, while the average GLP1 user will (assuming they keep taking it) be the same weight, or even a bit lighter.
renewiltord 7mo ago
Everything is discipline. If you just always do the thing you’re supposed to you will win at life. People can’t always do the thing they’re supposed to so they supplement with drugs that help them do it: caffeine, amphetamine, SSRIs, GLP-1RAs and related drugs. In fact, everything is discipline. If you were disciplined enough to always put the basketball in the net from anywhere on the court you’d be Steph Curry. The thing is most people don’t have that kind of discipline. Someone runs up to them and puts their hand up in the air? They shoot wide or balk. Curry shoots true. Discipline. Just always do the right thing and never do the wrong thing and you’ll be fine at literally everything.
- amazingamazing 7mo ago
  Some things require talent like your examples, weight loss does not imho. The disparities in obesity and culture within country says it all.
  - cthalupa 7mo ago

deleted 7mo ago

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storus 7mo ago

Isn't GLP-1 creating a "feel-good" starvation? Patching the receptors telling the brain one is not hungry and then just letting the body starve happily, leading to significant muscle loss and aged face? Contrary to e.g. water fast where the body switches to 100% ketosis that can run as long as there is any fat in the body and one supplements electrolytes (Mg/K/P/HCO3) and vitamins (predominantly B1/B2/B3), leading to a much more healthy appearance?

mrtesthah 7mo ago
There is nothing inherent in your description that would support your implied claim about facial aging.
- storus 7mo ago
  "Emerging research suggests GLP‑1 receptors are present on adipocytes and fibroblasts. Some animal studies indicate that GLP‑1 agonism may promote lipolysis in subcutaneous fat more aggressively than in visceral fat, leading to disproportionate loss of facial fat. It also may affect collagen synthesis or skin architecture, though human data are still evolving."
rootusrootus 7mo ago
GLP1s do not themselves cause any worse muscle loss than you would experience if you lost the weight by watching calories the old fashioned way. "Ozempic face" is almost certainly an artifact of people who spent their life significantly overweight having somewhat looser skin than they would if they had maintained a low weight throughout their life. Also, not everyone gets the face effect, not by a long shot.
- gedy 7mo ago
  Yeah exactly, what people call Ozempic Face is often just wrinkles. I look a bit older now that I lost 40 lbs, but much healthier shape. Fat does fill in your face some
  - deleted 7mo ago

r-johnv 7mo ago

This is the study that the article references. (The linked one on the post is an older study) https://bmjmedicine.bmj.com/content/5/1/e002150 https://bmjmedicine.bmj.com/content/5/1/e002150

jeremie_strand 7mo ago

[flagged]

camillomiller 7mo ago

We built a world where food is so processed and toxic that it makes you easily fat, but instead of fixing that we invented a drug that makes you eat less. Why not invent a drug that makes you less thirsty for those whose water is contaminated by fracking?

liv_intel 6mo ago

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