Ozempic shows anti-aging effects in trial

It's great because we had no other way to address this problem at a population level. Not any realistic ones, anyway.

Like, I figured we were just never going to solve it, given the two possibilities were "radically re-engineer US culture such that moving to the US doesn't make previously-skinny people fatter" (with other countries heading the same direction as us needing to make similar moves, one supposes) or "find a miracle drug". Neither seemed likely. Turns out, decent odds we've managed the latter! Which was always the more likely of the two, but I still wouldn't have rated it as very likely.

And not just weight loss, but the people I know on GLP-1's have also significantly cut back on alcohol. I think there are ongoing trials around GLP-1's and general addiction.

> Many people (will only speak to America), view being fat as a literal moral failing. Gluttony or overeating are not the sin, but being fat.

I feel like I've seen and heard more of the opposite: The trend is to avoiding anything that might make someone feel blame for arriving in their situation.

With obesity the trend is to blame some combination of "our food supply", trending science topics like microplastics or the microbiome, and genetics.

I've heard countless people explain to me that dieting doesn't work for them. It's not hard to find people claiming they ate <1000 calories per day and still gained weight. Even Eliezer Yudkowsky, a figurehead of the "rationalist" movement, has written about "metabolic disprivilege" and claimed that his genetics do not allow him to lose weight through dieting. This thinking runs deep.

What's interesting about GLP-1 inhibitors is that they modulate the intake portion of the diet, which shatters these previous notions that some people had "metabolic disprivilege" and simply could not lose weight by reducing caloric intake. They just make it easier to reduce food intake.

And also the idea that it is "easy" to lose weight is completely out of touch. If it was there wouldn't be millions of people trying hard, spending money on trying and failing for decades, and entire businesses addressing that.

RFK Jr's "let them eat less" is paradoxically the modern version of "let them eat cake"!

You can be gluttonous and still thin. I eat 2 lbs of ground beef a day, with tons of cheese on it. For breakfast I have 6-8 eggs, with cheese. I have my morning coffee with heavy whipping cream. For desert, I whip up some of the heaving whipping cream and have it with frozen berries thawed out. It drives gfs nuts but they're too anti fat to try it.

> Many people (will only speak to America), view being fat as a literal moral failing. Gluttony or overeating are not the sin, but being fat.

As an American with a sister with thyroid issues, I can say that is absolutely not true for the majority of Americans. People are mostly sympathetic to those who are not obvious slobs.

I'm not a Catholic, but wasn't the idea of an indulgence that God intentionally allowed an alternative path to redemption, such that if you buy an indulgence, you are (at least by their definition) worthy and deserving?

I always thought of this as essentially the same idea as with Civ allowing you different paths to victory.

The weight loss mechanism largely just comes from suppressing appetite though, so it still lines up with the penance for sin narrative. It’s not that different from wearing a hair-shirt and whipping yourself if you find yourself having lustful thoughts. Only instead of a whip you just feel kind of uncomfortable and nauseous if you eat too much.

>My opinion is to wait long enough to validate there are no long term harms, but beyond that, yeah, adjust the priors, it could be a modern aspirin.

it can be more than aspirin. Such an effect on glucose should, among other things, be affecting cancer, probably in a very positive way.

> Gluttony or overeating are not the sin, but being fat.

This is a strange thing to say. If you do something normal, and you end up in a normal state, why would that be a moral failing? There's no such thing as "overeating". Different people eat different amounts. The same person eats different amounts at different times.

> (From that perspective:)a miracle cure that allows someone to stop being fat is like an indulgence (in the Roman Catholic sense). It’s a cheat, a shortcut that allows the unworthy to reach a state they do not deserve.

This is incoherent. If you believe that being fat is a sin, but that the things you do that make you fat are not sins, then a miracle cure that makes you thin removes the only sin you were committing. You can't be unworthy if you're not fat. In order for a miracle cure to be "cheating", it is necessary that the sin is in the behavior and not the result.

> I would prefer if we figured out what other than cultural changes is making everyone have symptoms of inflammatory dysfunctions.

I personally hope it's just cultural and sugar/hfcs. Because some alternatives might be grim to reckon with just from a humanistic/grief perspective: https://pubmed.ncbi.nlm.nih.gov/34484127/

> That said, we are at a point where people are overweight enough that getting exercise has its own risks, and taking a medication that allows you to be more active is likely to cancel out some of those downsides.

And yet we rarely ask or say "maybe I should just eat fewer calories?" Unless you have some other disorder that prevents normal bodily function, that does work (and would be viable I'd imagine for the majority of people being prescribed).

But it requires patience and discipline which are basically non-existent for the majority of the population.

I think that's a completely reasonable concern to have, it doesn't seem to be the case wrt obesity but for the myriad of other potential effects it's important to keep in mind.

I think this might be revisionism. A lot of people feared early anesthesia because it was far more dangerous than today.

I also notice people will make note that 'eccentrics' from the 1940s-1950s hated air conditioning but it helps to understand it was a dangerous technology that regularly injured and killed people back then, especially in its earlier days the adults of that period were children during. AC didn't get safe until fairly recently in the 70s, 80s and 90s. It would catch fire or leak poison that killed people in their sleep. Some people just saw it as an unnecessary risk. Same with early fridges. When they leaked, that leak could be fatal as poison or explosion.

It wasnt until later that these technologies got safer and even now today, we consider full anesthesia a last resort and will always try to get away with local or twilight anesthesia because full anesthesia does regularly injure, disable, and kill people. Evolution didnt design us to be trivially "shut off" like this. Injecting us with substances like that will always come with risk.

In other words, a lot of those people weren't mindless luddites, but people who assessed their personal risk and said "nope, not worth it." I think that's perfectly fine.

I'd argue the revisionism of today and the ego justifications of the time were just that, ego protection. Its far easier to say "Well, I'm tough, I don't need that," then "I'm scared of that." The former is rewarded in our individualist capitalist society. The latter is vulnerability and honestly which is often only punished in a society like ours. We see it today with people with limited access and affordability to healthcare in the USA putting off care or engaging in various home remedies, alt-medicine, supplements, or conspiracy-culture-esque pharma drugs gotten cheaply via the gray market.

Are you talking about MMother Teresa? She wasn't that long ago...

Semaglutide is a signaling peptide, these are basically in a different class of medication that has traditionally been largely ignored. Partly due to difficulty defending patents for a class of medication that the body produces naturally, I.e. the instructions are in the DNA. Even if a drug company patents one GLP-1A they can’t patent all of them and any of them will work much the same way.

Because it’s a naturally occurring signaling peptide there already exist people who have too much of it and too little of it due to normal genetic variation.

> We also don't know what the long term side effects of it will be, if any.

The first GLP‑1 receptor agonist was commercially released in April 2005, meaning 20+ years. People who often repeat this: If 20-years, and tens of trials, isn't long enough to "know" then where is the line exactly?

Thalidomide by contrast was available for 4-years, Vioxx for 5-years, and Rezulin for 3-years by contrast.

> There's also something to be said for gaining the discipline to do it yourself along the way, which may lead to keeping more of the weight off in the long run.

That doesn't work; we know it doesn't work both from small and large scale studies, and population evidence since 1970s. So you're promoting the same thing we've been doing, and failing at, for beyond all of my lifetime. Feels like a religious belief at this point, rather than following the data and what we know from it (i.e. that objectively does not work, and has never worked).

Is there something new you know that health experts haven't known as Obesity as increase up through 40.3%+ (with overweight being 73.6%+)?

Or that's who you notice. My husband takes ozempic for type 2 diabetes and it completely fixed his blood sugar while causing very moderate weight loss.

What the people in this study have causes abnormal visceral fat accumulation in the belly and back and itself causes disturbing changes in body shape and appearance, does not respond or normal weight loss, and hasn't had real treatment options. That ozempic has beneficial effects for it in an RCT is actually awesome, it's the framing given by the headline that is bad.

I notice it in people who have never been the weight that they're suddenly walking around as, with them it often looks overdone, too thin for their features etc, but in those who have used it to get back to weights where I've seen them before...I didn't guess. They had to tell me.

Any means of attaining weight loss at a similar rate will tend to do the same thing. Especially if you’re starting from quite-heavy, not just dropping 20lb or something.

It varies. People are often thinner in their twenties than their thirties and forties. If you browse some before and after pictures the ones who have had their skin tighten tend to look younger for that reason alone.

That's just what happens when you get skinny. People who have always been skinny just look sickly always so we don't notice.

> Haven’t these types of drugs been in use for ~15 years?

The predecessor of semaglutide, liraglutide has been sold since 1998. GLP-1 has been studied since the 70s. The first human was injected with GLP-1 agonists in 1993 IIRC.

it could also suggest that BMI isn't a great metric, though, as has been in the news often lately.

regardless, thanks too.

Very interesting! Thanks for chiming in.