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

84 points by siquick 2 days ago | 122 comments | View on ycombinator

TaupeRanger 2 days 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 2 days 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 2 days 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 2 days 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 2 days 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 2 days 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 2 days 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 2 days 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 2 days 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.

jeremie_strand 1 day ago |

The same patern plays out with statins and antihypertensives — discontinuation events are well documented. The real question is whether we frame GLP-1s as a treatment 'course' or a maintenance medication, and the medical system seems largely unprepared for the latter.

r-johnv 1 day 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 2 days 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.

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mullingitover 2 days 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 2 days 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

camillomiller 1 day 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?

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nisegami 2 days 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

bethekidyouwant 2 days ago |

Studies get worse every year.

Aboutplants 2 days ago |

The most capitalistic drug ever! Take the drug forever and lose weight but stop taking it and you’ll die.

jryio 2 days 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.