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

https://nautil.us/whiplash-heart-attack-and-stroke-risk-jumps-when-people-stop-taking-glp-1s-1279029
44•siquick•2h ago
Study: https://pubmed.ncbi.nlm.nih.gov/39888616/

Comments

Robotbeat•1h 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•37m 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•29m 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•26m 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)

TaupeRanger•1h 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!!!"

rayiner•1h 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•51m 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•50m 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

post-it•47m 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•1h 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•56m 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.

bethekidyouwant•51m ago
Studies get worse every year.
jimbokun•35m ago
Or articles that try to convey the content of studies have always been poor and continue to be poor.
jryio•48m 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•45m 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•30m 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•27m ago
I don't think you read the study. The people returned to their pre treatment risk profile after ceasing treatment
cthalupa•11m 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.

bradleyy•43m 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.

nisegami•42m 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
0x3f•37m 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•34m 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•31m ago
The most capitalistic drug ever! Take the drug forever and lose weight but stop taking it and you’ll die.
devin•30m ago
That isn’t what this says at all.
mh-•12m 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.

Teknoman117•25m 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•23m ago
Hey, I can identify. Sending good thoughts your way.
cthalupa•21m 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•19m 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.
brap•18m ago
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.
amelius•6m ago
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.
mullingitover•18m 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.

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