[jaredklewis]

GLP-1s are miracle drugs that (to my mind) seem one of the great accomplishments of medicine along side things like vaccines and antibiotics. They are a cure for all manner of metabolic conditions.

How are they a “gamble?” For patients, their efficacy rates are stunning. If you meant from an investing perspective, Eli Lilly and novo nordisk have very down to earth valuations when compared with AI companies.

[tzs]

I don't know what OP considers to be a gamble, but one thing that comes to mind is that from what I've read most people who succeed at significant weight loss while taking GLP-1 drugs regain most or all of the weight within a couple years if they stop taking the drugs.

I'm in the US and if my doctor had suggested such drugs before last year I'd have been reluctant because (1) they were expensive even with insurance, (2) just how expensive varied quit a bit from insurance provider to insurance provider and from plan to plan from a given provider, and (3) as I said I'm in the US, and so never knew for sure who my insurance provider would be next year and even if it was going to be the same provider I never knew what their plans would be like next year [1].

Starting a new drug that looked like it would be a "rest of your life" drug where the price could change year to year from reasonably affordable to painfully expensive would definitely feel like taking a gamble.

Now I'm old enough for Medicare, and they are something I would at least consider because Medicare seems to be less volatile. They are still expensive, if my understanding is correct, with the need to meet a deductible and with copays or coinsurance, but all that counts toward the part D annual cap of $2100 so there is at least a cap making it somewhat safer to make long term plans. (But Republicans in Congress want to eliminate or at least significantly raise that cap, so long term planning is still somewhat of a gamble).

[1] In the US around 80-85% of people under 65 who have health insurance that is not provided through the government get their health insurance via their employer's benefits package. Most of the rest get it through the ACA marketplace. Employers often renegotiate plans with their provider or switch providers when the old plans/provider prices go up. The ACA market is even more volatile.

[1-more]

> most people who succeed at significant weight loss while taking GLP-1 drugs regain most or all of the weight within a couple years if they stop taking the drugs.

Anecdata: I've gone from 260lb down to a minimum of 198ish, up to maybe 230, back down to 193, long slow climb up to 270 and now on a GLP-1 I'm under 230 and definitely look fat, but in the right light you can see my quad separation. The only people I know who've lost the kind of weight I've lost and kept it off (like a 5' man going from 250lb down to 145) went from logging every bite in My Fitness Pal (or similar) to keeping the log running in their head of what they're eating all day every day. Diabetics sometimes say they're making their prefrontal cortex do the work of their pancreas. That feels relatable.

So IDK if there's a weight loss solution that works that you don't have to do in perpetuity. "Eat less" yeah sure, but how? Magic Danish Gila monster potion that makes you want to eat less, or recording everything you eat and using that to tell yourself you're more full than you feel?

[Balgair]

I agree that their large scale rollout will be very beneficial on the whole. The US is absurdly overweight and obese.

But these are powerful medications that affect very highly conserved areas of tetrapod biology. We discovered GLPs in the mouths of gila monsters, after all. So you then can infer that that the mechanism is at least 300 million years old (our last common ancestor with lizards).

Actually, I tried looking this up, and glucagon is likely 5-600 million years old, back to all chordates, the Cambrian explosion essentially, though likely even before that. So, incredibly conserved. Like, if you are a multicellular animal, odds are you have some glucagon-like thing for digestion regulation.[0]

We're strongly messing with a system that is just tremendously old. Biology and evolution are ruthless about this stuff, it edits it out as fast as it possibly can. That it's been so closely held is a very big sign for us that we need to tread extremely carefully.

Like, clearly, other countries do not have these issues with weight. Yes, they are developing them, I know. But even the US didn't have these issues near as bad just two generations ago, a blink in biological terms. You and I both know that the solution is not a pill, but the root cause of the obesity epidemic itself. These injections and pill are just band-aids for a much deeper and more pernicious problem.

But then again, you and I both know that we're not going to get at the root cause anytime soon either.

[0] This is biology so you'll find exceptions everywhere though

[Izikiel43]

> Biology and evolution are ruthless about this stuff, it edits it out as fast as it possibly can. That it's been so closely held is a very big sign for us that we need to tread extremely carefully.

As long as you have descendants, biology and evolution don't care, once that's done it's game over for them.

> That it's been so closely held is a very big sign for us that we need to tread extremely carefully.

It's been tested for over 20 years, the weight loss bit is the recent one.

> other countries do not have these issues with weight.

Yes they do, some are much worse than the US (https://data.worldobesity.org/rankings/), there are a lot of countries above 30% obesity rate.

> both know that the solution is not a pill

It's part of the solution, is how you help existing people with the issue.

Doing a restrictive diet is not easy (I know, I've been dieting since october, lost 15 pounds, but I can go on autopilot for this, which is not the case for others), it requires a lot of discipline that most people don't have, and our bodies are optimized to store calories, as well as being very efficient in consuming them, because for most of history famines were common, last ~100 years being the exception to the rule for most of the world population.

Future generations can be helped by better food culture and education, and that's the other part of the solution, long term.

[sylos]

The weight gain in the us compared to the rest of world is undoubtedly related to the callous disregard corporations posess for life in general, let alone the subtle things like microbiomes and fungi that shape our ecosystem