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There may not be a safe off-ramp for some taking GLP-1 drugs, study suggests

arstechnica.com

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Re: There may not be a safe off-ramp for some taking GLP-1 drugs, study suggests

#51

Post by orwin »

NitpickLawyer wrote: post #20
bryanlarsen wrote: post #7

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.

> we just don't know what it is. calories_in < calories_out seems to be a pretty good formula.

To a certain point yes, but also no. Depends on which fat you're talking about and which calories you are talking about (calories from carbs without fibers cost nothing to absorb, calories from fat cost more than half the energy they give you) (also if you have a good gut health, some calories are just never absorbed).

Calorie restriction works up to a certain point, and weirdly the benefits aren't linear, and almost flat for visceral fat(i.e: if you're using 2.6 kcal a day and eating 2.4 kcal, you will loose roughly the same amount of visceral fat than if you only ate 1.8kcal, and slightly more 'external' fat (that one you shouldn't care much if you're only interested in health)).

Calorie expenditure works linearly though, but it's hard to out-exercise your diet, and exercise while obese can be dangerous (my ankles still have to be reinforced despite me being under 24 BMI)

Re: There may not be a safe off-ramp for some taking GLP-1 drugs, study suggests

#52

Post by SpicyLemonZest »

aishsh wrote: post #35
perelin wrote: post #22

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…

> Given the general health benefits that are being observed with GLP1-s the only reason to get off them is costs imo There’s also the perverse incentives wrt broader society. Enabling the average person to control their physical health is orders of magnitude better for society and orders of magnitude less profitable than the current trends. Maybe a setup where glp drugs are nationalized and only used to further under…

What don't we understand about the obesity epidemic? The story seems pretty clear to me at this point:

* Almost everyone has access to a wide variety of delicious food, which we on average enjoy eating more of than is required to maintain a healthy weight.

* We don't want the government to forcibly restrict people's food access.

* Research consistently shows that voluntary portion control works occasionally in the short term and not at all in the long term.

* Many people have proposed specific ingredients or nutrient classes that can be adjusted in a person's diet to resolve obesity, but none to date have checked out.

In principle, I suppose, there could be some crazy diet hack we don't yet know about. But why should we expect that to be the case? To be honest, I think a lot of the existing discourse on this topic was just wishful thinking, because before GLP-1s the bottom line was not "some people need a pharmaceutical intervention" but "some people are just gonna be obese and there's nothing we can do to help them".

Re: There may not be a safe off-ramp for some taking GLP-1 drugs, study suggests

#53

Post by SpicyLemonZest »

Aurornis wrote: post #43
SpicyLemonZest wrote: post #38

Earlier quoted context omitted.

I dunno. It seems straightforwardly analogous to the fake medical marijuana clinics you see in places where recreational use isn't legal, or the countless online pharmacies with doctors on retainer to prescribe Ozempic and Viagra. It's not how I would design the medical system if I were in charge, but these aren't addictive substances like opioids.

Testosterone induces physical dependency which can be irreversible when taken for prolonged periods. I don’t think it’s analogous at all to medical marijuana.

Interesting. I'm surprised I didn't know that and have to agree that makes the analogy inapplicable.

Re: There may not be a safe off-ramp for some taking GLP-1 drugs, study suggests

#54

Post by neogodless »

tyleo wrote: post #4

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 testoste…

> not only regained significant amounts of the weight they had lost on the drug, but they also saw their cardiovascular and metabolic improvements slip away. Their blood pressure went back up, as did their cholesterol, hemoglobin A1c (used to assess glucose control levels), and fasting insulin.

This does sound like "reversion to the mean", but saying it's "regaining weight" may be missing the bigger picture. More like "losing all previously gained health benefits."

It's less clear how "unsafe" those regressions in health markers are.

Re: There may not be a safe off-ramp for some taking GLP-1 drugs, study suggests

#55

Post by Thegn »

csense wrote: post #37
sReinwald wrote: post #30

Earlier quoted context omitted.

Strange framing, isn't it? Bariatric surgery shows 25-65% significant regain rates depending on definition and timeframe. And regular dieting is even worse. Nobody would frame that as a safety issue. That's... just how weight loss works, not a unique GLP-1 problem. Calling a return of symptoms (obesity) a "safety issue" is like saying insulin has "no safe off-ramp" because diabetics get hyperglycemic when they stop t…

At some point, somebody at the site changed the title. The old title was "GLP-1 Drugs Improve Heart Health, But Only If You Keep Taking Them." How do I know that? The URL slug tells the tale. > Fear gets clicks, I guess I strongly suspect this is the reason the title was changed.

I know they (Ars Technica) do A/B title tests sometimes from discussion with one of the people who works there.

Re: There may not be a safe off-ramp for some taking GLP-1 drugs, study suggests

#56

Post by tyleo »

financltravsty wrote: post #42
tyleo wrote: post #4

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 testoste…

As an experienced polysubstance researcher, that's not exactly accurate. TRT cessation does not inherently cause men to have suppressed hormone levels after. With precautions and extra steps like HCG to maintain leydig cell/testicular function, preventing atrophy, one may safeguard against that risk. Coming off TRT, yes you will have lower levels as your HPTA has been suppressed by exogenous hormones. One may speed u…

This reasoning is not flowing through for me. It feels like you are saying:

1. There is an off ramp for TRTs but some people have, “true permanently lowered levels of hormones.”

2. For GLP-1s, “there is no off-ramp, but the only effects I’ve noticed are a return to my baseline.”

To clarify my original post, I consider the ability to return to baseline to mean there is an off-ramp and permanently impacted to mean there is no off-ramp.

Re: There may not be a safe off-ramp for some taking GLP-1 drugs, study suggests

#57

Post by Aurornis »

gadders wrote: post #44
Aurornis wrote: post #21

Earlier quoted context omitted.

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: (Source 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 busi…

>>The trick the clinics are using now is “diagnosing by symptoms”. You can't really diagnose by levels, though, unless you knew what that person's previous levels were. Setting an average across a population is not really realistic - you can't say Shaq should work to the same levels as, say, Emo Phillips. TRT is normally used due to aging, though, so you are unlikely to have your testosterone levels spontaneously rec…

If someone shows up with a testosterone level of 700 you can (and should) explain that low testosterone is not the explanation for whatever they’re suffering from.

The TRT clinics are ignoring levels or even not testing at all. They’ll find an excuse to prescribe to someone even who has clinically high levels because they want the monthly recurring revenue from keeping that customer for life.

Re: There may not be a safe off-ramp for some taking GLP-1 drugs, study suggests

#58

Post by orwin »

Each time an article on glp-1 is out, I will comment:

Yes, you can loose weight without it, I did, I'm even in the healthy range now.

No, you don't have to, if you need medicine help, take it.

When I lost weight, I had my first real job that I liked so much, it didn't felt like one, 11 weeks of vacation per year, a nice enough apartment I couldn't be evicted of, great emotional support and advices and support from a doctor.

The only thing draining my willpower every day was the calorie restriction, and nothing else to worry about.

If you're in a similar spot I was, maybe trying a diet without glp-1 is better since we don't have any long term study on it yet, but if you're not: obesity will destroy your body more than any long term side effects can. Please take them if you can afford it.

The only thing I earned beside uncomfort and pain when I lost weight without drugs are internet points on hacker news, and the ability to say 'i did it' (also glp-1 didn't exist, so less long term health issues from obesity). Honestly if I had to redo it, I would take the drug despite a similar situation. Weight loss is hard, and not being able to do it without help is not an indictment on you or your character, but on your situation.

Re: There may not be a safe off-ramp for some taking GLP-1 drugs, study suggests

#59

Post by chimeracoder »

Aurornis wrote: post #57
gadders wrote: post #44

Earlier quoted context omitted.

>>The trick the clinics are using now is “diagnosing by symptoms”. You can't really diagnose by levels, though, unless you knew what that person's previous levels were. Setting an average across a population is not really realistic - you can't say Shaq should work to the same levels as, say, Emo Phillips. TRT is normally used due to aging, though, so you are unlikely to have your testosterone levels spontaneously rec…

If someone shows up with a testosterone level of 700 you can (and should) explain that low testosterone is not the explanation for whatever they’re suffering from. The TRT clinics are ignoring levels or even not testing at all. They’ll find an excuse to prescribe to someone even who has clinically high levels because they want the monthly recurring revenue from keeping that customer for life.

> If someone shows up with a testosterone level of 700 you can (and should) explain that low testosterone is not the explanation for whatever they’re suffering from.

I'm not going to say TRT clinics are the best actors here, but to an actual endocrinologist, diagnosing hormone issues isn't so simple as looking at single point-in-time measurement of total testosterone.

Testosterone levels naturally vary even for a given individual - two readings at the same time of day on different days even a short period apart can be dramatically different - and that's not even taking into consideration the fact that total testosterone levels aren't the sole (or even primary) mechanism for diagnosing androgenic endocrine issues.

Re: There may not be a safe off-ramp for some taking GLP-1 drugs, study suggests

#60

Post by taeric »

fwip wrote: post #39
taeric wrote: post #32

Earlier quoted context omitted.

Yeah, I would fully support "easy" there, but regaining weight isn't something most people think of as danger.

Many people who are losing weight are doing so because they're concerned about their health, right? Especially heart health.

I mean, sure? But this is like saying there is no safe way to get old. Which, is kind of accurate. But not what people think of when you say safe.
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