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Comment by tjohns | Hacker News Reader

Studies have show most people rapidly regain the weight once they stop taking GLP-1 drugs.

The dysfunctional biochemical processes that contributed to overeating are still present if you discontinue the drug. Your body has a natural set-point for the weight it wants to be at, and the hunger and food noise comes right back as your body tries to get you back to your old weight.

It's possible that after after a long enough time at a healthy weight your body's natural weight set-point will regulate itself back down. But this process take years.

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"You'll regress if you stop taking the drugs" may be true, but it seems like a double standard to frame it as a knock against weight loss drugs when this also describes countless other interventions for chronic issues...

Your lupus will flare up again if you stop taking Plaquenil! Your eyesight will be bad again when you take off your glasses!

I actually agree entirely.

I'm just being objective in stating that the evidence suggests that these drugs need to be taken long term to have lasting effects. Not everyone realizes this.

But I think that's okay if it can get people back down to a healthy weight. The health impact from being overweight is serious, and we know that lifestyle intervention has a stunningly abysmal success rate.

Anything we can do to reverse the obesity epidemic is a good thing.

More than fair :) I may have jumped to conclusions there because I generally see that line of thinking from people who go "...and therefore there's no point in taking meds," but you're right that not everyone realizes these are long-term drugs.

> It's possible that after after a long enough time at a healthy weight your body's natural weight set-point will regulate itself back down. But this process take years.

I've spent a fair amount of time pursuing obesity research and I've never seen that. The closest I've seen is researchers or studies mentioning "Maybe the set-point resets are x years" but never seen any direct evidence of this.

Is the idea of a set-point settled medical/scientific fact, or still a disputed theory?

It's still a theory. We definitely don't know the underlying mechanism(s) of action, and it's likely there's more hidden complexity there.

But rapid weight gain after weight loss (until you arrive somewhere near your old weight) is at least a well observed experimental effect. About 80% of people who lose weight, through any means, will revert back to their old weight.

Source:

https://www.ncbi.nlm.nih.gov/books/NBK592402/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3673773/

i lost about 30 lbs a couple of years ago, white knuckling my way through starving myself on a medically supervised diet. within two months of going off the diet, i was back at the exact weight i started at, to the pound, and haven’t varied >2lbs since, no matter what i eat. consider me convinced on the setpoint theory.

Set-point theory is pretty much settled medical fact. The mechanism involves leptin, and you can easily see processes that defend bodyweight change in both directions. Though it will more aggressively defend weight loss than weight gain.

In addition prey animals will defend against weight gain more aggressively than non-prey animals. Which makes sense from an evolutionary standpoint. If a lion gets fat he doesn't have nearly as much to worry about than if a gazelle gets fat.

A lion may also have to endure long periods of no food.

There are lots of physiological parameters with set-points, such as body temperature. The problem for weight gain/loss is that instead of one set-point for body weight itself, you have maybe 5-10 set and operating points that are indirectly related to body weight, but not direct measurements of it. They don't all have to be "working right" to keep you healthy, but if too many become disordered at once, you're gonna have a problem.

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