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!!!"
https://bmjmedicine.bmj.com/content/5/1/e002150
The data on the results section shows almost parity between the control group and participants who discontinued for 2 years.
Note that while it is a well conducted study at the US VA with 300,000+ patients, it is not a randomized study so fully eliminating confounding variables and reverse causality is hard.
It’s like stopping a blood pressure medicine and then being surprised that people have more heart attacks afterwards.
> 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/10.11...
Which makes sense since we have strong evidence for the GLP-1s providing significant protective benefit even without weight loss.
GLP-1 masks the problem and people don't realize their actions aren't ideal once the mask is removed.
The issue is shameless "science" reporting like this which packages up the results for non experts, without explaining the nuance because they know the sensational headlines will get more attention, and they know non-expert readers will get scared and share the article on places like HN or Facebook.
It's such an obvious play: find one doctor who'll make a loaded statement with the word "whiplash", write on this one study as if it's gospel truth, get everyone reading it as scared as possible. Throw in links to other emotional articles like "Can you die of a broken heart?" throughout the text to trigger secondary emotional reactions that will get confused with the main ones. Boom, social media sharing heaven, who cares if the science was valid or not?
And to be clear, the science underneath might be valid, probably even is, but it would need the expertise of someone who understands statistics and medicine to decide whether you should take action based on this or not.
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.
> 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
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.
The first year was the most dramatic loss of 100lbs. I was miserable and didn't know what I was doing other than counting calories. The rest of it was more considerate of total nutrition, and that's what made my good eating habits stick.
I say this because while I'm not a doctor I think GLP-1 is probably unnecessary for the vast majority of patients. Better food and information is more available than ever before.
I would strongly advise to watch your A1C and get out of the diabetes danger zone if you are. Most people can drop a few percent in as little as 6 months and it makes a massive difference in mental health. Blood glucose has a direct impact on the brain and overall cardiovascular health. If you drink alcohol, you might want to take a break also to let your liver/kidneys/pancreas do their jobs properly and restore insulin sensitivity and other hormones. Look into the "fruit paradox", and more generally get a good salad in for lunch to address nutrient deficiencies. Not crappy salads either. You're not a rabbit. Treat them like the amazing sandwiches without bread that they are.
Sounds like old advice, because it is, but I find people aren't listening because they want to more deeply understand why to do it and what the effects are. Convenience and unintuitive pricing are false bargains that get in the way of healthier habits. Focus on nutrition and not quantity. Change your groceries, change your life.
We have mountains of evidence that willpower fails for something like 99% of everyone, which is far from a vast majority. I applaud anyone's efforts to become healthier, however (though 240 at 6'1" is still obese, I would still explore medicine if I could not get any lower "naturally").
I am in a totally different setup than you though - 225 weight, goal to get down to 180 (my Army weight was 170.) I exercise a lot, and lost 30 pounds through diet two years ago. But it was the hardest thing I've done since Ranger school! So paintful to not eat enough. Gained it all back. I'm in month one of tirz and it is as easy as pie.
It really opened my eyes to just how food centric society is.
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…
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.
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.
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.
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.
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.
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?
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.
Oh wow it's so simple! why has nobody thought of this before??
> 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.
"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.
There are two modes the human body operates normally - insulin-driven, active when carbs are in the food, and ketone-driven, active when there is a lot of fat storage and no food intake, or food has no carbs. Insulin-driven operation switches to starvation when food intake has caloric deficit but still enough carbs for insulin to be triggered; ketones on the other hand lead to zero insulin activity and pure fat burning; starvation is only activated when humans reach around 4% body fat while in ketosis.
It might result in more loss of buccal fat than otherwise but even that is not definitive. Activating the receptors is not the same as burning fat - there are GLP-1 receptors all over your body in all sorts of organs. If you activate them in your brain you're not burning your brain for energy.
I can still do my routines easily with no issues. My muscles look slightly smaller I think, but maybe that's the fat around them that's been diminished.
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.
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.
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.
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.
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.
