[radu_floricica]

I said "reasonable side effects". I was _not_ trying to suggest that drugs have no side effects or need no consideration when taking them. Tylenol can give you a pretty horrifying death if you misuse it.

But this reinforces my main point - if we ended up comparing ozempic with ibuprofen, we definitely lucked out. Considering the benefits it offers it might be worth taken by some people even if it was on the level of chemotherapy.

[rscho]

Ozempic is very recent. Given the volume of prescription, the probability of problematic side-effect in the short-to-medium term indeed seems low. But it sill is too early to say whether ozempic really isn't problematic. Let's hope so.

[cthalupa]

I really don't understand this skepticism around semaglutide and long-term effects.

One, GLP-1s are not a new class of drug. We have had them in various forms for about two decades now.

Two, the clinical trials have followed the standard sort of schedule as any other medication we release. I don't hear or see all the hand-wringing that these have received over every other medication we develop.

Three, they are analogs to hormones our bodies already produce. They're not some totally alien substance that we have zero understanding of. We modify them to have longer half-lives, bind more strongly/weakly to certain receptors, etc., but it's not like these are significant departures from things our body already handles day in and day out.

Yes, maybe there is something specific to semaglutide or tirzepatide or the newer generations of GLP-1 medications that we don't understand that has some sort of long term effect. But what is the foundation for that worry? Exenatide has not shown any of those concerns in two decades of use. Basically every single health marker that changes when on these drugs changes in (often profoundly!) positive ways. It makes significant positive impact on the cause of the single largest increased in all-cause mortality for the Western world. Newer generations are even more promising - retatutride has shown significant anti-cancer impacts on rodent studies, and mechanistically the pathways it is acting on there work very similarly in humans, so there is strong reason to believe that will carry over. Even the modern generations have a huge list of benefits that take place basically immediately upon beginning to take them, even without significant weight loss, including protection against CVD-related incidents such as heart attacks, strokes, and deaths related to them.

What we know today about all of the positive impact they have, mechanistically how they are doing it, and the data we have on this class of medication being used in general... the side-effects would have to be hugely detrimental and in a way that just doesn't make much sense based on our current understanding.

It's not impossible, of course, but worrying about it seems silly unless your general stance is that you won't take any medication until that specific formulation has been on the market for decades.

[radu_floricica]

I think some viewpoints just sound wise, and get repeated a lot. Being skeptical about medication is one of them.

A legitimate worry, one Taleb might be bringing up, is that we should hold Ozempic to a higher standard because it's being taken by many people, and any problems it has down the line will have a much larger impact. But that 1. is happening anyways and 2. is not influencing an individual decision to take it or not, it's a society thing.

[rscho]

> silly unless your general stance is that you won't take any medication until that specific formulation has been on the market for decades

Yes, I'd argue that this is the default stance for many healthcare professionals.

[cthalupa]

I'm sure it is the default stance for some.

Many is hard to quantify. In my experience it is not the majority, nor is it a stance that makes much sense to me in general.