[wonderwonder]

I would think eventually all of the additional positives of the drug will resolve to obesity is bad and reducing obesity has health benefits. Which should be perfectly fine as its valid and results in massive positives in both health and quality of life.

[estearum]

We already know that's not the case though. A huge portion of the benefits are downstream of obesity, yes, but we already know GLPs have positive effects even without weight loss.

[wpasc]

genuinely curious if you have some sources I can read on the subject? most of the benefits/papers I've seen have not touched on or included studies for patients on GLP's where weight loss was ruled out as the factor?

[AWebOfBrown]

https://www.medlink.com/news/from-blood-sugar-to-brain-relie...

[nwienert]

Actually even in the very beginning I saw numerous studies showing effects outside weight loss, I'm sure a search would find them. I remember seeing at least 3-4 a couple years ago.

[astura]

>eventually all of the additional positives of the drug will resolve to obesity is bad and reducing obesity has health benefits.

This is not true.

Ozempic appears to affect the brain's rewards system and its known to decreased cravings and urges for a range of unhealthy behaviors, from alcohol consumption and smoking to gambling and shopping to nail biting and skin picking.

Beyond that, Ozempic appears to lower the risk of heart attacks and strokes in overweight people well beyond what weight loss alone would explain. Maybe due to the above (less drinking and smoking) or another unknown mechanism of action.

https://www.scientificamerican.com/article/weight-loss-drug-...

[toraway]

I started taking prescription Zepbound (tirzepatide) right when it was approved for about 6 months and lost 30 pounds, later switched to a low dose of much cheaper grey market semaglutide for maintenance. The anti-drinking side effect was unexpected and somewhat shocking to experience. I had heavily drank in the evening for almost a decade to varying degrees and then pretty much stopped overnight once hitting the 5mg dose of Zepbound on the second month. After ending the Zepbound I had a few months where I wasn't taking anything before resuming the maintenance semaglutide, and although food cravings slowly started returning, I still had/have zero interest in drinking whatsoever unless in a social setting where I may have 1-2 drinks (but usually avoid it altogether without requiring any conscious effort).

There is definitely massive variance in the individual psychology/biology that leads to habitual alcohol overuse so I'm sure others might not have the same experience. But for me I'm pretty confident that breaking that deeply engrained habit of starting the first of 6-10 drinks at 6-7pm every day was what did it (without feeling like I was being forced to do something I didn't want). Which was pretty much impossible for me to even envision back when it was such a normal part of my day-to-day coping strategy for stress/depression/etc.

Although I always knew my drinking was excessive and terrible for my health, past my early 20s I was super high functioning and wasn't interfering with my job or life (other than holding me back and probably slowly killing me), and so being an "alcoholic" was never part of my identity (rightly or wrongly), which I kinda think ironically made it easier to just take the win and move on with my life without nagging self-doubt or fixation on whether my "addiction is cured".

But it's been about 2 years now and I hardly ever think about alcohol even when super stressed so something, somewhere in my brain changed thanks to tirzepatide and whatever the mechanism I'm grateful for that happy accident of a positive side effect!

[aucisson_masque]

> later switched to a low dose of much cheaper grey market semaglutide for maintenance.

Do you plan on staying on a 'low dose' of semaglutide Ad vitam æternam ?

I'm asking because I believe that's one of the negative of these kind of drugs, it's effective at losing weight but as soon as you stop you gain back all the weight whereas learning to eat healthy is slower but more durable.

[nwienert]

I remember I saw a meta review that claimed in the abstract that "analysis showed a rapid regain of weight after cessation of therapy", but then looking into it deeper actually quite a bit of weight loss was retained even many months after stopping.

In my personal experience I've now known about 12 people who've taken it and stopped, and none have "rapidly" regained, in fact many have retained most of their loss for significant periods of time. Most people gain weight over a long period of time (from lets say early teen to their current age).

What happens when they stop is a very slow return to baseline gain. So if it took them 10 years to become obese, then it takes 6-12 months to lose it all with Tirzepatide, you'd expect it would take them 10 years again to regain it.

People act like this is some sort of addiction, but I don't think so - and I'd bet that a "refresher" that was only a small % of the year would keep most people completely at baseline, and they could even slowly taper that down.

[toraway]

For me at least it definitely wasn't quite so abrupt, it was probably about 2.5 months before I noticed the trend line ever so slowly moving up. Pre-Zepbound I had already lost about 30 pounds from my max weight of 260ish thanks to a strict Keto diet I began at the beginning of COVID lockdowns which was a lot of effort to maintain long term, so when I saw I met the criteria for my insurance to cover Zepbound I was like "sure, why not?".

I'd probably just go back to Keto if I decided or was forced to stop a GLP-1a completely. Keto was the first and only way I've had success losing weight in my life. But once the initial novelty wears off it takes a lot of discipline to stick to and continually avoid the pressure from friends/family to eat with everyone else. I'm also vaguely concerned about cholesterol impact long term doing it for life, but relative to obesity probably still a good trade off.

It's definitely doable though, I did it for 2 years so I know the drill and that's my fallback. But not being obese is much more enjoyable than being obese, and it's a lot easier to exercise at a normal weight, so I don't have much interest in going back to 260 pounds. If that meant taking a drug for life, so be it unless it turns out to cause turbo-cancer or something.

I mostly eat "healthy" foods by preference (and habit from growing up in a "health food" family), but for me my problem is managing portion control while never feeling completely full at the target calories per meal/day. Which can feel pretty miserable to stick with especially comparing to others in my family who more or less eat the same foods but don't have that problem at all. Keto was so effective because I actually felt "full" (at the expense of excluding a lot of otherwise healthy but carb-rich foods).

Taking Zepbound definitely reshaped my perception of obesity though, compared to Keto which required constant, intense self-enforced discipline avoiding 4/5 of any menu, being on a GLP1-a and able to eat what everyone else is eating but just stop and not feel hunger pains or cravings convinced me the attitude of "fat=lacking discipline" is antiquated and ignores real variance in how different people experience hunger/satiation.

[aucisson_masque]

> Taking Zepbound definitely reshaped my perception of obesity though, compared to Keto which required constant, intense self-enforced discipline avoiding 4/5 of any menu, being on a GLP1-a and able to eat what everyone else is eating but just stop and not feel hunger pains or cravings convinced me the attitude of "fat=lacking discipline" is antiquated and ignores real variance in how different people experience hunger/satiation.

Well I always assumed that people are fat because they are eating too much...of the wrong thing.

I lost 10kg not long ago, 20 lbs in American, and never ever i did feel hungry. Quite the opposite, i would be stuffed to the nose on fruits, vegetables and meats.

And believe me when I tell you I ate like an ogre.

I challenge anyone to actually gain weight on eating only vegetable fruits and meat. After losing these 10kg, I tried to gain 15kg of muscle and overeat on this regime to the point to want to vomit, couldn't gain weight. When I added fat and cereals, weight increased so fast I had to slow down.

With the average caloric expenditure being 2200 kcal for a normal healthy man, not even doing sport, the average vegetable being 300 kcal per kg, it means you would have to eat 7.3kg (16lbs) of vegetable per day.

I don't know you personally but I can safely say that you can't eat 16 lbs of vegetable per day, or 5lbs per meal. It's physically impossible.

So yeah I guess that how people experience hunger/starvation could play a role, but it's not the full story.

[toraway]

(too late to edit but I forgot to include)

A couple years before starting Zepbound I had tried a prescription for naltrexone for 3 or 4 months to reduce drinking which had pretty much zero effect for me. Naltrexone apparently helps for some people and has a similar theorized mechanism acting on reward/pleasure but didn't do anything to break that habit of pouring a drink within the first hour I was back home.

I might have drank slightly less as it was slightly less enjoyable but did nothing for the habitual element which for me was much more problematic than how the alcohol made me "feel" subjectively or the exact number of drinks I had per night.

[stavros]

This is probably unrelated, but I used to play a lot of DotA for years (at some points for 12 hours a day), then quit cold turkey, then started again last year, but maybe 30-60 minutes a day.

After I started Mounjaro, I haven't really had the urge to play at all. I played a game a few weeks ago but I was kind of "meh" about it, and haven't played since. It's striking.

[silexia]

What does excite you instead now on the medication?

[stavros]

Making stuff, big time. I love making things with hardware, software, or 3D printing.

A few friends and I made a maker community, and over the weekend I made a semi-automated newsletter for links we post in our Discord (https://themakery.cc). I really had fun doing that, it was great.

Last few weekends, https://encyclopedai.stavros.io/, https://theboard.stavros.io/, https://pine.town/, and a few other bits and pieces.

[SubiculumCode]

I am generally a person that has a few beers each week. I haven't had a beer in a month since starting GLP-1. It just never sounded appealing.

[SubiculumCode]

It is a reasonable thought, but that exact question has been investigated and benefits were not totally explained by weight loss. I don't recall the link, but it was featured on HN

[flir]

Nah, obesity reduction is itself a downstream effect of messing with neurotransmitters. There have to be other consequences of that - both good and bad.

[estearum]

There don't have to be any other consequences, certainly not both good and bad ones. Biology doesn't actually have some scale of justice that means good things must be offset by bad things.

But yes, it's very probable (in fact we already know) the drug is doing several things in the body.

[flir]

I was more thinking that evolved systems rarely have convenient switches you can flip and just get a single outcome. You perturb the system, and you get a cascade of changes. It's not like engineering.

Nothing about justice was implied, so lets say desirable and undesirable instead of good and bad.

[estearum]

Yes you’re right to be concerned about this, I’m taking issue with your assumption that there must be undesirable effects.