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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

#31

Post by Aurornis »

mise_en_place wrote: post #28
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…

By what mechanism? That's not how it works. LH and FSH are suppressed when you're on TRT, but they stabilize after cessation. The question is, why would someone with clinical hypogonadism cease TRT?

> That's not how it works. LH and FSH are suppressed when you're on TRT, but they stabilize after cessation.

The testes atrophy over time when LH and FSH are suppressed. Even if LH and FSH return (which isn’t guaranteed) the testes need to be able to respond to those hormonal signals, but atrophied testes do not respond the same.

For someone with true intractable hypogonadism this hardly matters because they weren’t capable anyway. Many people prescribed TRT today don’t actually have intractable hypogonadism, though.

Body builders have some tricks to try to reverse this, but it’s not perfectly effective and even body builders know to cycle their steroids to avoid having prolonged periods of suppressed HPG axis activity. I was involved with weightlifting in my younger years but never dabbled with steroids or TRT. Everyone I know who did try testosterone or steroids thought they were doing it the safe way (HCG, PCT, limited cycle length) but became unable to produce enough endogenous testosterone by their 40s even with SERMs.

Men on TRT for years will have considerable testicular atrophy that is not totally reversible.

> The question is, why would someone with clinical hypogonadism cease TRT?

TRT is no longer limited to men with clinical hypogonadism. Men’s health clinics that advertise on social media, TV, and radio will prescribe to anyone who contacts them (and pays cash for the prescription and gear). In some surveys of patients on TRT, 1/4 of patients didn’t even have testosterone levels measured prior to initiation of TRT.

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

#32

Post by taeric »

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…

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

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

#34

Post by mise_en_place »

Aurornis wrote: post #31
mise_en_place wrote: post #28

Earlier quoted context omitted.

By what mechanism? That's not how it works. LH and FSH are suppressed when you're on TRT, but they stabilize after cessation. The question is, why would someone with clinical hypogonadism cease TRT?

> That's not how it works. LH and FSH are suppressed when you're on TRT, but they stabilize after cessation. The testes atrophy over time when LH and FSH are suppressed. Even if LH and FSH return (which isn’t guaranteed) the testes need to be able to respond to those hormonal signals, but atrophied testes do not respond the same. For someone with true intractable hypogonadism this hardly matters because they weren’t…

> TRT is no longer limited to men with clinical hypogonadism. Men’s health clinics that advertise on social media, TV, and radio will prescribe to anyone who contacts them (and pays cash for the prescription and gear). In some surveys of patients on TRT, 1/4 of patients didn’t even have testosterone levels measured prior to initiation of TRT.

That's hugely problematic if true. They should be investigated and if found of wrongdoing, have their medical licenses revoked.

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

#35

Post by aishsh »

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 understand why we have an obesity epidemic and eventually finance changes to combat it? Ideally the drug makers would do this without requiring government intervention, but I doubt they will.

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

#36

Post by Mistletoe »

saurik wrote: post #9
Mistletoe wrote: post #3

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.

> 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 o…

Yes I can see that completely, but we see the data doesn’t support it. The issue was biological all along.

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

#37

Post by csense »

sReinwald wrote: post #30
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…

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.

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

#38

Post by SpicyLemonZest »

mise_en_place wrote: post #34
Aurornis wrote: post #31

Earlier quoted context omitted.

> That's not how it works. LH and FSH are suppressed when you're on TRT, but they stabilize after cessation. The testes atrophy over time when LH and FSH are suppressed. Even if LH and FSH return (which isn’t guaranteed) the testes need to be able to respond to those hormonal signals, but atrophied testes do not respond the same. For someone with true intractable hypogonadism this hardly matters because they weren’t…

> TRT is no longer limited to men with clinical hypogonadism. Men’s health clinics that advertise on social media, TV, and radio will prescribe to anyone who contacts them (and pays cash for the prescription and gear). In some surveys of patients on TRT, 1/4 of patients didn’t even have testosterone levels measured prior to initiation of TRT. That's hugely problematic if true. They should be investigated and if found…

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.

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

#39

Post by fwip »

taeric wrote: post #32
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…

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.

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

#40

Post by Aurornis »

mise_en_place wrote: post #34
Aurornis wrote: post #31

Earlier quoted context omitted.

> That's not how it works. LH and FSH are suppressed when you're on TRT, but they stabilize after cessation. The testes atrophy over time when LH and FSH are suppressed. Even if LH and FSH return (which isn’t guaranteed) the testes need to be able to respond to those hormonal signals, but atrophied testes do not respond the same. For someone with true intractable hypogonadism this hardly matters because they weren’t…

> TRT is no longer limited to men with clinical hypogonadism. Men’s health clinics that advertise on social media, TV, and radio will prescribe to anyone who contacts them (and pays cash for the prescription and gear). In some surveys of patients on TRT, 1/4 of patients didn’t even have testosterone levels measured prior to initiation of TRT. That's hugely problematic if true. They should be investigated and if found…

It’s true. You can even go on Reddit and find anecdotes and guides about which clinics to call and what to say to get prescribed with minimal hassle.

Some of the clinics were even prescribing anabolic steroids intended for terminal cancer patients.

If you want to read about something even crazier, look up the services that were started during COVID to be prescription mills for Adderall or Xanax. The relaxed COVID prescribing rules allowed telehealth providers to give schedule II prescriptions to new patients remotely, so services were created to advertise on TikTok and give prescriptions for a monthly fee. The FDA cracked down on these, though.

There’s even a famous story of a whistleblower who worked at one of these clinics and got reprimanded for not prescribing Adderall enough. There was a leaked memo where they pushed providers to prescribe Adderall over other options because their data showed the highest customer retention rate that way.

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