Discontinuation and reinitiation of dual-labeled GLP-1 receptor agonists (nautil.us)

by siquick 122 comments 86 points
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122 comments

[−] TaupeRanger 57d 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!!!"

[−] r-johnv 56d ago
They actually do compare against a control group. This is the study that is being referenced.

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.

[−] gpt5 57d 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.

[−] watermelon0 56d 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/10.11...

[−] cthalupa 56d 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.

[−] techjamie 56d ago
A tale older than the use of GLP-1. People do X to lose weight, they hit a target weight, declare victory and continue the habits that got them in trouble in the first place. You can go a little bit heavier on the meals and loosen the exercise if you desire, but you still have to keep yourself within maintenance threshold or the weight comes back.

GLP-1 masks the problem and people don't realize their actions aren't ideal once the mask is removed.

[−] smallnix 56d ago
It's not useless. It might be expected, but now it's more certain. This allows planning with it.
[−] rayiner 57d 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.

[−] Teknoman117 57d 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 57d 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.

[−] Robotbeat 57d 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.
[−] 46493168 57d 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.

[−] ldayley 57d 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.
[−] storus 56d 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?
[−] Aboutplants 57d 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.
[−] camillomiller 56d 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?
[−] r-johnv 56d 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

[−] 0x3f 57d 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.

[−] nisegami 57d 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
[−] mullingitover 57d 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 57d 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

[−] liv_intel 43d ago
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[−] jeremie_strand 56d ago
[flagged]
[−] bethekidyouwant 57d ago
Studies get worse every year.
[−] Aboutplants 57d ago
The most capitalistic drug ever! Take the drug forever and lose weight but stop taking it and you’ll die.