Those drugs let people experience intermittent fasting and fasting by reducing hunger and snacking.

The danger of suppressing hunger signals is that hunger could've been a important que for nutritional needs.

Muscle loss is severe danger of gpl-1, And muscle size is tied to longevity.

So although promising it's not without danger. And there are other paradigms but those are not yet explored yet the underlying mechanisms work the same.

Edit: Let's keep HN a place where discussion can be held without just kneejerk down voting.

Almost certainly at the weight loss dosages people are taking now, but semaglutide (at least) can be tuned up and down for effect. Time will tell what kind of dosage is required for these non-weight-loss benefits.

That said, I think it's more important to focus on how this drug works -- it works in the brain and in specific areas of the brain that we now know are important for weight loss/addiction/inflammation(?) (because of these emergent miracle drug effect). It doesn't seem outside the realm of possibility that drug companies will be able to target these systems with more finesse in the future as opposed to superdosing engineered stable GLP-1 molecules that flood the system.

It is the future understanding of what this drug does that is the real promise for all people -- we are just in the early stages of understanding what we've found.

But that puts us back in the "telling people to exercise doesn't cause them to actually do it" at the public health level. For you yourself, you can simply live a less risky, healthier life. For all yous, probably we need something like a once-weekly pill or injection that doesn't require drastic habit changes. For all of society on a forever timescale, of course, we can ignore the fact that adults won't change their ways and focus on instilling lifelong athlete habits in kids. Doesn't seem to be the direction we're going in, though.

https://en.wikipedia.org/wiki/GLP-1_receptor_agonist

Glucagon-like peptide-1 (GLP-1) receptor agonists, also known as GLP-1 analogs, GLP-1DAs or incretin mimetics, are a class of anorectic drugs that reduce blood sugar and energy intake by activating the GLP-1 receptor. They mimic the actions of the endogenous incretin hormone GLP-1 that is released by the gut after eating.

https://archive.today/YgiWx

On GLP-1 agonists, you don’t get nearly the counterbalancing reduction in energy expenditure you usually see with caloric restriction. Your body keeps happily releasing lipid stores, assuming they will be replenished, but they aren’t. Hunger hormones remain untriggered, cortisol stays low, and insulin keeps shuttling glucose into cells to be burned.

If you aren’t metabolically deranged, your body does this anyway. But many people have totally decompensated metabolically due to excess energy intake over time, and essentially cannot recover without some kind of treatment.

GLP-1 is just the beginning — future compounds will do a better job maintaining muscle mass, for example. But this is looking like an absolute miracle, and once patent protection ends (especially for oral formulations), we’re going to be living in a very different world health-wise.

It's really interesting to me that there's some evidence for Metformin -- a diabetes drug that suppresses glucose production and appears to do other things we don't fully understand -- having general health benefits and possible life extending benefits in healthy people. Normally it's just used to treat some forms of diabetes.

Feels like we're on the cusp of figuring something out about inflammation, aging, and metabolism.

Because evolutionary fitness doesn't care about what we care about, and even if it did it operates so slowly it hasn't yet finished adapting to us having invented cooking.

That said, I share your skepticism. This kind of story feels almost exactly like the old Victorian (literal) snake oil advertising: https://commons.m.wikimedia.org/wiki/File:Clark_Stanley%27s_...

In short: the reason that the human body wouldn’t have evolved to make more GLP-1 automatically yet is because evolution causes populations of organisms (not individuals) to change, over generations, to be better suited to their environment.

And 50-100 years is nothing in terms of evolution. We spent 500k years evolving to optimize gathering every calorie we can. And then yesterday it turned out that maybe it is in fact possible to have too much.

Also, the human body does make some GLP-1 itself. Maybe it was just getting started.

Because we haven't had the infinite years required to "just evolve" every possible bodily improvement?

I don't know if it's an ideal wonder drug or also has downsides we haven't found yet or some of the positives are misinterpreted but if "why didn't we just evolve it" was meaningful it could be an argument against ANYTHING being good in the way presented.

That's easy to answer. We exist today in a very different environment to that we evolved in.

It makes perfect sense that there could be a hormone that wouldn't provide a net reproductive benefit to hunter-gatherers or subsistence farmers but provides an immense health benefit to sedentary humans eating unlimited food. In fact, it would be surprising if there wasn't.

Replace "GLP-1" with any of: aircraft, computers, buildings, WiFi, ...

Some things are easy for nature to find and some things aren't!

And even of the things that are easy for nature to find, and that we would have found useful even in the environment of evolutionary adaptation, they might not confer overall fitness if they are too costly.

When it was just appetite suppression, that made sense, we're not adapted to a modern degree of plenty. Not sure that explains the other positive effects, if these results reproduce.

This exactly. There was a recent paper about Ozempic and (IIRC) dementia that saw that the drug acted implausibly quickly to prevent illness -- the Kaplan Meier curves were literally separated at day 0. [1]

Confounding is rampant in this area. The people who published the paper I linked below should not be scientists. It's embarrassing. Anyone who cites it in support of Ozempec as a miracle drug has revealed that they don't know what they're doing, and should be ignored, with prejudice [2].

More generally, it's depressing that so many people are piling on here to tell you that you're wrong, based on little more than their "knowledge" that obesity is bad. The fact is that most of the science around GLP-1 agnoists and anything other than obesity is weak, to say the least.

[1] I believe it was this paper. Certainly, the KM curves in this are ridiculous: https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz...

[2] Sadly, this appears to include the "Alzheimer's Association"...though you sort of understand why they're biased in favor of miracles.

EDIT: I am just now realizing that Derek Lowe is citing this paper. Oy vey.

My sister takes Ozempic and is the proto-typical obese white girl with way too many kids she can't afford and only eats trash. It probably saved her life.

I don't think that humans eat to obesity by default. People have had adequate food for quite long and not grown fat.

Maybe there is something in out environment or our foods that are blocking the GLP-1 receptor? If a modern food company discovered something like that they'd immediately realize that (unintentionally) they sell better, probably without realizing what they had created.

Honestly? I'm not much of a physiologist, but based on the effects regarding addictions like tobacco or narcotics that cannot be causally downstream just of diet, I'd wonder if GLP-1 agonists aren't actually impacting stress-interoception systems rather than just hunger and metabolism. Under that hypothesis, the evolutionary reason would be: because we evolved to undergo stress mostly in physically strenuous, energy-burning situations, while high loads of cognitive and emotional stress without physical effort are a novelty to post-industrial lifestyles.

Even if folks gain tolerance that doesn’t seem overly concerning. Mental health drugs also have tolerance issues and changing medicines every few years, while it has challenges for the patient, is an accepted part of long term psychiatric treatment.

A lean current-epoch human -- with our food abundance, access to modern medicines, higher standards of life, lower risks of injury, etc -- is likely going to be markedly healthier than a non-lean current-epoch human or a lean human from a prior age where medicine/food/etc was worse.

Or is it, in fact, the direct result of the drug?

Will it happen soon enough to prevent population collapse due to plummeting fertility rates? Will fertility rates go even lower or will the population start to rise again as deaths fall? Will we see stagnation due to older brains being stuck in their ways, or will we be able to fix that too?