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!!!"
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.
>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.
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.
> 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.
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.
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.
It lets me more or less skip a meal but holy hell I am craving sugar more than ever. On the whole I'm cutting calories and have lost a lot of weight, I just wish I didn't want sugar this much.
I’ve always been more of a savory kind of person myself. I’d take biscuits and gravy or a steak over sweets any day!
But I feel you on sugar. Took me a long time to cut sugar cravings. A decade ago I cut regular soda out of my diet, which a few years later led to me cutting out pretty much anything sweetened. Realistically it wasn’t the sweetness for me, it was the “mouthfeel” or doing something with your mouth. Just straight sparkling water satisfied the entire craving for me.
The hardest thing for me to give up / heavily cut back on was fried things. Maybe that’s the result of my parents using french fries as the reward food when I was a kid…
You missed out on both of the weight suppression tricks, which really does suck. Appetite suppression (or reduction of food noise) is pretty useful, but GLP1s also tend to punish you mightily if you overeat. For me, even if I were hungry, overeating will make me hurt for hours. I could not gain weight on this even if I wanted to.
There are some difference, too, between the various drugs. I never tried ozempic, I went directly to tirzepatide (zepbound). And then to retatrutide. I will say that reta is in some ways the most interesting, because it has less appetite suppressing activity than tirzepatide (this is common, not just me), but it still cuts my stomach capacity quite a lot, and ramps up my metabolism. I had stalled at about 90 pounds down with tirzepatide, and reta immediately knocked off another 15. I track calories, and I had changed nothing. Felt more hungry, still lost more weight. Wild.
From one rando to another, I recommend trying tirzepatide. Or try semaglutide again but stacked with cagrilintide -- some people get pretty great results with that, similar to tirz.
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.
Wegovy/Ozempic didn’t do anything for me for months. Then my doc put me on Tirzepatide+Phentermine combo and I forgot what being hungry even feels like.
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.
Which do you like? Barebells salty peanut and chocolate dough over here. Though the sugar alcohols certainly aren’t great for you either, I think they were recently linked to stroke risk
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.
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)
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.
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.
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.
> 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.
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
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.
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.
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.
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
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.
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.
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.
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!!!"
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.
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.
>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.
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.
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
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.
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.
It lets me more or less skip a meal but holy hell I am craving sugar more than ever. On the whole I'm cutting calories and have lost a lot of weight, I just wish I didn't want sugar this much.
I’ve always been more of a savory kind of person myself. I’d take biscuits and gravy or a steak over sweets any day!
But I feel you on sugar. Took me a long time to cut sugar cravings. A decade ago I cut regular soda out of my diet, which a few years later led to me cutting out pretty much anything sweetened. Realistically it wasn’t the sweetness for me, it was the “mouthfeel” or doing something with your mouth. Just straight sparkling water satisfied the entire craving for me.
The hardest thing for me to give up / heavily cut back on was fried things. Maybe that’s the result of my parents using french fries as the reward food when I was a kid…
You missed out on both of the weight suppression tricks, which really does suck. Appetite suppression (or reduction of food noise) is pretty useful, but GLP1s also tend to punish you mightily if you overeat. For me, even if I were hungry, overeating will make me hurt for hours. I could not gain weight on this even if I wanted to.
There are some difference, too, between the various drugs. I never tried ozempic, I went directly to tirzepatide (zepbound). And then to retatrutide. I will say that reta is in some ways the most interesting, because it has less appetite suppressing activity than tirzepatide (this is common, not just me), but it still cuts my stomach capacity quite a lot, and ramps up my metabolism. I had stalled at about 90 pounds down with tirzepatide, and reta immediately knocked off another 15. I track calories, and I had changed nothing. Felt more hungry, still lost more weight. Wild.
From one rando to another, I recommend trying tirzepatide. Or try semaglutide again but stacked with cagrilintide -- some people get pretty great results with that, similar to tirz.
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.
Wegovy/Ozempic didn’t do anything for me for months. Then my doc put me on Tirzepatide+Phentermine combo and I forgot what being hungry even feels like.
Hey, I can identify. Sending good thoughts your way.
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.
Did you try those zero-sugar candy bars (often labeled as protein bars)? They work quite well for me, no messing with GLP-1 necessary.
Which do you like? Barebells salty peanut and chocolate dough over here. Though the sugar alcohols certainly aren’t great for you either, I think they were recently linked to stroke risk
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.
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.
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)
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?
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.
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.
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.
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.
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
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.
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.
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.
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.
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
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.
Studies get worse every year.
Or articles that try to convey the content of studies have always been poor and continue to be poor.
The most capitalistic drug ever! Take the drug forever and lose weight but stop taking it and you’ll die.
That isn’t what this says at all.
(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.
What do you mean? All of the comments that misunderstand the study are downvoted from what I see.
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.
Doesn't it make sense that, if you were taking a drug that reduces morbidity, you'll get increased morbidity if you stop it?
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.
I don't think you read the study. The people returned to their pre treatment risk profile after ceasing treatment
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.
You failed to understand the results of the study and quoted a passage that does not in any way support your assertion.