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!!!"
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.
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.
So, why not? Seems very obvious to everyone here on HN that it's "kind of useless" unless they did have that, yet they didn't. What reason would there be for ignoring that?
> 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.
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 couldn't hit my macros on tirzepatide - couldn't get enough protein without feeling sick to my stomach. One of the reasons I swapped to reta.
(though as a general note for anyone reading, just getting enough protein isn't enough - you need muscle stimulus too. Getting enough protein will help reduce the amount lost but if you really want to stop it, you gotta do resistance training)
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…
Try allulose-sweetened stuff. Allulose is a sugar your body doesn't metabolize like sucrose. It has zero calories and does not increase your blood sugar. It's a component of maple syrup and so does taste a bit maple-y, but better than most artificial sweeteners and even stevia leaf extract (stevia and aspartame have a "tang" to them I dislike).
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.
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
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.
Similar experience here with Tirzepatide. Overeating is punished swiftly and painfully.
If it works for you, look into getting one of the 15mg pens and counting clicks in order to get more doses per vial. I've been on the one pen for 3 months now and it's still got plenty of juice left.
Yeah I might just have to go get it out of plan. Kaiser covers Ozempic, but none of the Tirzepatide based medications.
I am a big guy (6’4, 330 lbs), but I was amazed that Ozempic just seemed to do nothing. I was having the gastric side effects, but I could still eat 3000 calories a day if I cheated without feeling anything.
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)
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.
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.
> 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.
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.
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.
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
A decade or so ago, when I was still in uni, I managed to get similar results naturally too - ~100kg down to ~65kg in around 18-24 months just by eating healthy and exercising more.
I put back all of that weight and then some during the COVID pandemic (I'm in Melbourne, Australia - we had the worst lockdowns on planet Earth) and this time struggled for years to lose it until trying GLP-1 drugs a few months back.
For me, what made it harder the second time around wasn't so much of a difference in discipline skills (if anything, they've improved) but the fact that there was so much more going on in my life - young family constantly getting sick, small business that started struggling, relationship/social issues, health issues (sleep apnoea) etc. etc.
I'd get on the weight loss train, lose a couple of kilos, then the whole family would get sick with the flu and I'd put it all back on again while recovering. Or maybe I'd be forced to shift my focus to the business so that we could keep the lights on. Or any number of things.
I guess my point is that it's not difficult to lose weight naturally (or any self-improvement, really) in and on itself, but it's completely different ballgame when you're fighting a war on 6 different fronts. Having one of those problems simply just disappear through GLP-1 drugs genuinely feels like a miracle.
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.
If you can be disciplined about taking a drug you can about food. How do you explain correlations in obesity across cultures? Genetic superiority? Again, imho just making excuses for laziness. The same logic you’re applying here also applies to even taking the drug and picking up refills from the mail…
Also look at obesity rates across time within the same country. It’s clearly not an issue of discipline, it’s an issue of what’s being eaten.
Why in the world do you think that taking a once a week injection requires even remotely similar levels of discipline to dealing with daily hunger and food noise? There's like, a dozen orders of magnitude in between. This is a silly argument.
> How do you explain correlations in obesity across cultures? Genetic superiority?
Every developed nation in the world except Japan has been seeing obesity and overweight rates rising at significant rates, including countries that have fairly similar cultures, such as Korea. You also see people move to America and stay in relatively isolated pockets of their culture and still gain weight.
So no. It's a matter of access to hyper palatable calorie dense food. The more of it around, the more likely people are to get fat. The fatter you get, the more of a feedback loop you end up in for a wide variety of known and relatively well understood mechanisms. GLP-1s help short circuit that feedback loop.
You just have to be disciplined to always shoot accurately at the basket. Most people send it one way or the other but if you are disciplined enough in your aim at the basket no matter the constraints you will be the best basketballer of all time.
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.
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).
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.
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.
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!!!"
It’s like stopping a blood pressure medicine and then being surprised that people have more heart attacks afterwards.
Which makes sense since we have strong evidence for the GLP-1s providing significant protective benefit even without weight loss.
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.
That does appear to be the case, according to the study.
> 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.
So, why not? Seems very obvious to everyone here on HN that it's "kind of useless" unless they did have that, yet they didn't. What reason would there be for ignoring that?
> 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
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.
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.
(though as a general note for anyone reading, just getting enough protein isn't enough - you need muscle stimulus too. Getting enough protein will help reduce the amount lost but if you really want to stop it, you gotta do resistance training)
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…
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.
If it works for you, look into getting one of the 15mg pens and counting clicks in order to get more doses per vial. I've been on the one pen for 3 months now and it's still got plenty of juice left.
I am a big guy (6’4, 330 lbs), but I was amazed that Ozempic just seemed to do nothing. I was having the gastric side effects, but I could still eat 3000 calories a day if I cheated without feeling anything.
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.
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)
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.
> 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.
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.
> 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.
I’m most curious about someone like me vs someone who lost the same amount on glp1 with respect to these stats
A decade or so ago, when I was still in uni, I managed to get similar results naturally too - ~100kg down to ~65kg in around 18-24 months just by eating healthy and exercising more.
I put back all of that weight and then some during the COVID pandemic (I'm in Melbourne, Australia - we had the worst lockdowns on planet Earth) and this time struggled for years to lose it until trying GLP-1 drugs a few months back.
For me, what made it harder the second time around wasn't so much of a difference in discipline skills (if anything, they've improved) but the fact that there was so much more going on in my life - young family constantly getting sick, small business that started struggling, relationship/social issues, health issues (sleep apnoea) etc. etc.
I'd get on the weight loss train, lose a couple of kilos, then the whole family would get sick with the flu and I'd put it all back on again while recovering. Or maybe I'd be forced to shift my focus to the business so that we could keep the lights on. Or any number of things.
I guess my point is that it's not difficult to lose weight naturally (or any self-improvement, really) in and on itself, but it's completely different ballgame when you're fighting a war on 6 different fronts. Having one of those problems simply just disappear through GLP-1 drugs genuinely feels like a miracle.
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.
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.
Or do you think that somehow genetics don't play one of the largest roles in your ability to be disciplined when it comes to food?
Also look at obesity rates across time within the same country. It’s clearly not an issue of discipline, it’s an issue of what’s being eaten.
> How do you explain correlations in obesity across cultures? Genetic superiority?
Every developed nation in the world except Japan has been seeing obesity and overweight rates rising at significant rates, including countries that have fairly similar cultures, such as Korea. You also see people move to America and stay in relatively isolated pockets of their culture and still gain weight.
So no. It's a matter of access to hyper palatable calorie dense food. The more of it around, the more likely people are to get fat. The fatter you get, the more of a feedback loop you end up in for a wide variety of known and relatively well understood mechanisms. GLP-1s help short circuit that feedback loop.
Now there’s something we agree on. If only we could agree that no one is stuffing cheeseburgers down people’s throat other than themselves. So close.
Once the shame around disgusting fattening food has reached a critical mass the problem will solve it self.
Ironically the excuses you make for them only worsen the issue. If fat people and the food they ate were appropriate shamed they both would cease.
FYI in Japan fat people are ruthlessly bullied. Fat people are rare. Food for thought, pun intended.
Stop tolerated junk.
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.
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).
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!
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.
To use a dense analogy: if I stopped brushing my teeth I would not expect to die of gum disease.
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.