There may not be a safe off-ramp for some taking GLP-1 drugs, study suggests
22 comments
·November 26, 2025tyleo
Interesting. Saying, "there may not be a safe off-ramp," doesn’t feel quite right. The article describes people losing weight while on the drugs and then regaining weight after stopping them. That's not ideal, but it does imply an off-ramp, just with regressions.
Compare that to something with no real off-ramp: testosterone replacement therapy. Once you're on TRT, you can permanently suppress your body's own testosterone production, and many men won't produce enough on their own afterward.
gtirloni
If you're on TRT, you are already not producing enough on your own.
Aurornis
Unfortunately that’s not true any more. TRT over prescribing is a major problem right now.
Studies of TRT patients have even shown that 1/4 of TRT patients may not have had their testosterone levels measured before being prescribed TRT: https://pmc.ncbi.nlm.nih.gov/articles/PMC6406807/ Completely unacceptable given how cheap testosterone testing is, but its happening.
TRT clinics have also become a big business. Their business model relies on prescribing TRT to anyone and then charging them monthly or quarterly to continue receiving those prescriptions, which as the parent comment noted become physically necessary after TRT causes the testes to atrophy.
theptip
But TRT suppresses endogenous production further, so if you go off it you’re worse than when you started.
tortilla
Unless you went on when you weren't really low because the men's vitality clinic pushed you into a treatment protocol*
* not me but I see it with men in my age range
PartiallyTyped
I am a big fan of Dr Rohin Francis, and this landed on my youtube's front-page recently
glp1guide
> Of the 308 who benefited from tirzepatide, 254 (82 percent) regained at least 25 percent of the weight they had lost on the drug by week 88. Further, 177 (57 percent) regained at least 50 percent, and 74 (24 percent) regained at least 75 percent. Generally, the more weight people regained, the more their cardiovascular and metabolic health improvements reversed.
So weight loss was actually maintained for most people -- the hard part is finding a healthy daily lifestyle which can maintain the drastic effects of GLP1s.
This information isn't new -- weight regain has been studied before and I've written about it before:
https://glp1.guide/content/do-people-regain-all-the-weight-l...
The missing piece to this article is just how bad the alternative is -- never having the cardiovascular and metabolic benefits is clearly not the best strategy (and if simply changing patterns was so easy, people would have done it already).
GLP1s don't work for everyone but they're pretty close to miraculous in effect given the balance of positive and negative side effects. Making GLP1s cheaper & more tolerable then figuring out how to actually deal with the complex web of how to keep the weight off sustainably for most people seems like the right way forward here, not avoiding potentially life-saving medication because you may not be able to get off of it as fast as you want (if you can afford it).
BTW, there is already generic Liraglutide, and legal workarounds for getting compounded Semaglutide that already mean no one pays the $1000 that was in the zeitgeist a while ago. Even Lilly Direct and similar outfits from Novo sell for $500/month, with the $150/month pricing coming soon[0].
[0]: https://glp1guide.substack.com/p/negotiations-are-underway-f...
pajamasam
For comparison, there also doesn't seem to be a "safe off-ramp" for obese patients from other weight loss interventions either: https://pmc.ncbi.nlm.nih.gov/articles/PMC4396554
bryanlarsen
The headline doesn't seem to match the article? 20% of participants did keep the weight off and 40% kept half the weight off after stopping.
So there appears to be an off-ramp, we just don't know what it is.
NitpickLawyer
> we just don't know what it is.
calories_in < calories_out seems to be a pretty good formula.
elevation
> regained significant amounts of the weight they had lost on the drug [...] blood pressure went back up, as did their cholesterol, hemoglobin A1c [...] fasting insulin
These symptoms will be familiar for anyone who has lost weight dieting and then returned to eating junk food.
samlinnfer
>have unhealthy habits that causes weight gain
>stop taking weight loss drug
>regain weight
>there is no safe off-ramp for GLP-1
I guess taking weight loss drugs don't really teach healthy eating habits.
petercooper
"Generally, the more weight people regained, the more their cardiovascular and metabolic health improvements reversed."
You don't say ;-) I lost 50 lbs and have kept it off for the past year while maintaining great BP. But I'm under no illusions GLP-1 medications don't have dangers and cause problems for many. It should be handled on an individual basis like any serious medication.
That said, is someone losing a lot of weight then gaining half of it back worse than them just staying where they were? I don't know the answer to that one.
quesera
> losing a lot of weight then gaining half of it back
The trick, of course, is to repeat the process as you asymptotically approach your goal.
Zeno's paradox of mass.
Mistletoe
There doesn’t need to be an off-ramp they just have to take it for life. Why would someone think they would keep the weight off? If they could they would have before Ozempic.
saurik
> Why would someone think they would keep the weight off? If they could they would have before Ozempic.
I think the intuition many people have--which I am not at all defending as correct, but it certainly isn't so obviously wrong that we should scoff at someone for thinking it works this way--is more like "if my weight was stable before I did this intervention, I just need to lose the weight and then my weight will once again be stable after it"; in this mental model, one would assume you only need lots of willpower to lose weight: after, you only will need as much willpower as you already know you have to not gain it back, as it isn't as if you are gaining weight currently.
rhines
I could see it building habits that persist even when no longer using the drugs. They've found other things to fill their time instead of eating, and things which would previously trigger them to start eating now trigger them to do other things.
There's of course a risk that when they stop the drugs that hunger will drive them to re-establish those habits, but now that they have new habits that fight that hunger they are in a much better position to resist it than they were when they'd initially established their eating patterns.
eps
> take it for life
That's literally the implication of these findings.
But one can always hope for a miracle drug that you can take for a bit, then stop, and have its effects last. Now we know that Ozempic is not that drug.
RankingMember
I think it would almost need to be some sort of genetic modifier, which may not be that far off.
unethical_ban
I imagine the idea for some is "if I can just get myself healthier, I can then stay motivated to maintain the healthier lifestyle required to stay skinny without the drugs"
constantcrying
Or an alternative title: "36 months of tirzepatide permanently treated obesity in 17.5% of patients."
I think that it is quite unsurprising that without the drug a large amount of people revert to their previous behavior and with that will revert to their previous weight.
As a GLP-1 user im really surprised that this is newsworthy. The mechanism of how these drugs lead to weight loss is appetite reduction. On GLP-1s -> less appetite, off GLPS-1s -> more appetite. Given the general health benefits that are being observed with GLP1-s the only reason to get off them is costs imo. They are absurdly expensive. Hope this will change in the next 10 years with patents running out and generics being available for cheap. The actual cost of production seem to be quite low. Gray/black market has them available for around a tenth of the otc price.