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Comment by linsomniac | Hacker News Reader

>There's a miracle drug powerful enough to robustly lower people's all cause mortality

Did I misread the article, my TL;DR of the article is that GLP-1 reduce the indicators or mortality without modifying the actual mortality (because most users return to normal indicators within about 2 years).

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> because most users return to normal indicators within about 2 years

Because they stop taking GLP-1s after 1-2 years, not, it seems, because the meds stop working.

They do? I was under the impression people stopped taking them because they’re massively expensive. And weekly injections is a bit annoying (though should be less annoying than diabetes or death or whatever else).

There is a set of the population, and not a small one, that will quit the drug as soon as they hit the weight they feel is good enough. Even if they can afford it and are used to the shots they just feel that it is done and don't feel like they'll rebound (although most do) once off it.

No, it's a miracle drug that drops mortality by a ton. The indicators aren't being faked. The weight causes the mortality, and the weight loss reduces it, and the weight regain reintroduces it. GLP1RAs introduce some noise to the indicators but not enough to cause what you're implying.

It's a maintenance medicine, not a cure, so if people stop taking it, they return to the same problems they had without it.

And it's under-commented upon because it's counterintuitive, but most people stop taking it. Like, two year continuation of use is about 25%.

That's kinda wild, because it seems like holy shit if you're taking a drug that lets you drop 10-20% of your body weight from obese down to normal why would you stop taking it, but people do.

Side effects? Also many might not be able to afford it long term as it's quite expensive.

Cost is a big factor. When it becomes generic then I suspect people will stay on it for a lot longer.

Because they're now "normal", so why would they continue paying for it, taking unpleasant injections, and enduring the side effects?

In this sense it's like any diet: they "work", but if you don't permanently modify your food intake, the weight comes back as soon as you go off the diet.

Another way of putting it is that people achieve their goals and wind down the usage of the drug that got them there.

I think that in a few more years the number may stay at 25% (or whatever) but that the makeup of the 25% may be different. That is, people will go off it and back on it if they see their progress reverse but that will happen to different people at different times.

Because the pharmacy will refuse to sell it to you.

Source: UK based friend who says the pharmacy will refuse to sell them once they fall under BMI 25 (still overweight). They'd prefer to be on the tiny maintenance dose but it seems to be very hard to achieve (unless you're going off the market completely).

I'll dispute that, I work for one of the online pharmacies and we won't stop selling it to you once you've reached BMI 25. We do have criteria to guard against sudden or extreme weight loss, but I think the BMI criterion for that is something like < 20 BMI (don't quote me on that, as I'm not sure, but it's not 25).

We'll also keep you on a small maintenance dose if you want, that's a conversation you'll have with your clinician and they'll judge whether it's medically appropriate. As far as I know, there's usually no reason to prevent you, though.

My friend orders from Medexpress - could you maybe share at least the first letter of your pharmacy or a hint so we can try to guess the name of the helpful one?

I don't think it's possible to send dms here....

Oh, it's Numan. If your friend has a different experience with us than what I describe, please email me and I'll look into it (email in profile or just username at Numan.com).

As far as I know, though, you can move to us from another pharmacy even with a BMI of < 25, as maintenance has different criteria than new prescription.

I'm not a clinician, though, so I may be wrong. If you want to email me, I can ask the clinicians and tell you for sure.

Thank you so much. Well try to reach out the normal way. Thank you, you've been so helpful already.

Because it costs $1000/mo and insurance wants to make it as hard as possible to get that covered because they cannot afford to pay $1000/mo * 45% of Americans without doing things to their rates that are forbidden by the ACA and, for that matter, any approximation of good sense. If people cannot afford an additional $450/mo each on average for their health care, how do you cover a critical long-term $1000/mo drug that 45% of the population needs?

Gating it behind mandatory expensive, difficult-to-schedule appointments with a specialist who is in abruptly short supply where the insurance company is doing their damndest to kick as many of them off their network as they can without getting caught to keep the shortage going is certainly part of that strategy. And the result is “people do not stay on the drug”, which is their goal, and if they don’t meet that goal they have an even bigger problem and can’t continue to exist as a functioning company.

Is that the cost in the U.S.??

Yup. Without insurance, GLP-1s can be up to $1,200/month.

The simple fact is, when it comes to drugs, the development is basically paid for by Americans.

You can also think about it the other way - if a drug caused you to lose 10-20% of your body weight, and you're now at a good body weight after 2 years, why would you want to lose another 10-20% body weight?

I understand that's not really how it works, but people often go very much by feel more than anything else.

> if people stop taking it, they return to the same problems they had without it

Source? Everyone I know who stopped taking it rebounded a bit, but not to where they were. And no literature shows 100% rebound to my knowledge.

I mean roughly in reference to the underlying mechanism it directly addresses, not all the downstream effects. And even that was, admittedly, sloppy, because there's some complex feedback loops involved. I guess it would be more accurate to say it is a maintenance medicine and not a complete cure, and so stopping taking it unmasks the continuing condition that is treating.

> stopping taking it unmasks the continuing condition that is treating

Some of the prediabetics I knew who stopped taking it (N = 2) stopped being prediabetic (N = 1).

I mean, yeah. You could always just lose weight and probably get out of being prediabetic.

> just lose weight

This might be the left-wing analog of climate denialism.

What does the left-wing or more broadly, political philosophy have to do with that statement?

It's not like it's impossible unmedicated. Plenty of people have and will do it. Obviously most people are unable to. I was always surprised just how few prediabetics did though.

"If we assume about 65% of people who start GLP-1 medications quit by the end of year one, that creates a big problem. When someone stops the medication, they'll usually regain the weight they lost, and in two years, most of those key health indicators (like BMI, blood pressure, blood sugar and cholesterol) bounce back to their starting point. "

So in addition to the quitters returning back to normal after they got life insurance underwritten when they were healthy, we have the unknown of the longevity of people on the glp-1 drugs.

Except for extreme obesity, it is about the same as people not on the drugs . Even moderate obesity only lowers life expectancy by a few years in men and about none in women. of course, quality of life will may be worse. Obesity only meaningfully lowers life expectancy at a BMI of 40-45+ for men

I meant: we don't know the longevity effects of people being on a glp-1 drug for decades.

Subtly different: you read "most...return to normal...within 2 years", it says "When someone stops the medication, they'll [return to baseline]"

Then from there, I click through the 65% #, assuming they have a good study on 65% of people stop after a year. Nah, they don't. It's super complex but tl;dr: specific cohort, and somehow the # getting on it in year 2 is higher than the # of people who quit in year 1.

I have a weak to medium prior, after 10m evaluating, that the entire thing might be built on more sand than it admits.

Lot of little slants that create an absolute tone - ex. multiple payouts over the "lifetime" of a life insurance policy. (sure, it's technically possible)

Also there's no citation for the idea this mortality slippage happened because of GLP-1, and it's been out for...what...a year? Maybe two?

That's an awful lot of people who were about to die, saved in the nick of time by...losing weight? Again, possible, I'm sure it even happened in some cases.

Enough to skew mortality slippage from 5.3% to 15.3%?

I thought they were 98% accurate?

Wait...is the slippage graph net life increase slippage? Or any slippage?

Because it's very strange this explosion happened in exactly the year of a global pandemic that had sky-high mortality rates for older people.

Since it's so new, of course there aren't any long-term data on GLP-1 takers. However, relying on prior knowledge about people who are good on the metrics, it can be presumed that they will do fine. And won't create financial risk for the insurer due to passing on earlier than expected. But only if they keep taking their meds and/or fix any underlying behavioral and health issues that made them obese in the first case!

Regarding the graph about slippage: yes, that looks like the Covid peak. However, even assuming this recent trend is an anomaly, the industry is in a changing landscape and needs to adapt. New metrics and criteria, and the fastest mover will capture the market. Business as usual.

I don't feel sad except for the people who managed to bring their health issues under control and now can't get life insurance.

GLP-1 isn’t new - the first trials were 20 years ago & there’s a lot of long term data from its use in diabetes management, prior to the weight loss application.

Ok, sure - but are diabetes patients representative of the whole target market for GLP-1? And there will still be an uncomfortable variable that controls the outcome - patient compliance. That's what makes life insurers woozy.

I didn't have look on the studies but I would not be surprised if a decent amount of participants were completely healthy individuals. And maybe (more from random sampling) some unsuspicious mildly overweight without other problems. Especially in the earlier cohorts of testing.

Right, you should read it though, we're in the weeds over here, it's not just sort of free-assocating chat, we're picking apart specific things about the article. One of them, as I mentioned 4 up, is that the study with the 65% # is confounded because the groupings involve type 1 diabetes, and also, the number rebounds higher than the # who stopped

I've been on GLP-1 for a month and my triglycerides halved, and my cholesterol dropped to the levels it was in my twenties. If that's not a predictor of lower mortality, there's something wrong with our fundamental medical knowledge.

Has your weight dropped?

Yes, I lost around 4kg. Though the triglycerides and cholesterol are mostly because I stopped eating sweets and fatty foods, not because of the weight loss itself.

I agree! (is this responding to part of my comment? :) )

Oh hmm, I may have replied to the wrong comment!

The slippage part of the article is definitely bogus. The origin of the graph [0] attributes it to Accelerated Underwriting programs.

[0] https://www.swissre.com/reinsurance/life-and-health/l-h-risk...

The drugs do not reduce mortality much or even at all. Such drugs may improve quality of life though. Except for severe obesity, 40+ BMI, life expectancy is not lowered much in men and even less in women in the setting of obesity. It's just that being obese makes all sorts of markers worse, yet people do not die much sooner. It's more about improving quality of life.

I guess similar to smoking a handful of cigarettes a day? (Not a whole pack. More like five.)

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