[AlphaAndOmega0]

I would appreciate citations. I'm a doctor on GLP-1s,who had previously convinced my mother to commence the same. In her case, it was driven clearly by failure of other methods to control her obesity and worsening liver fibrosis, on top of pre-existing diabetes. On my end, no such issues at present, but I consider it safe enough that it's a first-choice approach to robust weight loss, and I personally use it in conjunction with diet and exercise.

"Relatively high levels of significant side effects" is a vague and unhelpful claim:

High compared to what? What counts as a significant side effect here? What actually are the side effects in question? Are those side effects permanent and irreversible? Can they be avoided by adjusting the dose? Dozens of such considerations come into play.

No drug I'm aware of is perfectly safe, and I know many drugs indeed.

To the best of my knowledge, the combined risk of taking semaglutide utterly pales in comparison to the clear and present harms of obesity. The only clear downside is cost, and while I'm lucky enough to to have access to cheaper sources, they're not even that expensive when you consider the QOL and health benefits.

[friendzis]

https://pubmed.ncbi.nlm.nih.gov/38629387/

> Conclusion: Semaglutide displays potential for weight loss primarily through fat mass reduction. However, concerns arise from notable reductions in lean mass, especially in trials with a larger number of patients.

That's a significant long-term damage to health, quite possibly permanent for 40+ patients.

[AlphaAndOmega0]

Sounds scary doesn't it? It's a shame that the magnitude of lean-muscle loss is entirely comparable to that of going on a strict diet or fasting:

Intermittent/time-restricted fasting

https://jamanetwork.com/journals/jamainternalmedicine/fullar...?

That's simply how the body reacts to a caloric deficit, without additional exercise. If you combine both IFT and resistance exercise, you find no muscle loss at all:

https://pmc.ncbi.nlm.nih.gov/articles/PMC7468742/

That's an apple to oranges comparison, because there's nothing preventing someone from taking Ozempic from exercising on the side.

And in fact, other trials found that the overall ratio of fat:muscle lost was rather favorable, and that functional strength wasn't compromised:

https://dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.157...

>Based on contemporary evidence with the addition of magnetic resonance imaging-based studies, skeletal muscle changes with GLP-1RA treatments appear to be adaptive: *reductions in muscle volume seem to be commensurate with what is expected given ageing, disease status, and weight loss achieved, and the improvement in insulin sensitivity and muscle fat infiltration likely contributes to an adaptive process with improved muscle quality, lowering the probability for loss in strength and function*

Interpreting the risks and benefits of medication isn't a trivial exercise, if you're driven by a handful of studies or ignorant of the wider context, then it's easy to be mislead.

[friendzis]

> That's an apple to oranges comparison, because there's nothing preventing someone from taking Ozempic from exercising on the side.

Strongly disagree on this. If there was nothing preventing the patient from changing their diet and physical activity / exercise level they could lose the fat through diet and exercise without resorting to taking semaglutides in the first place. Withdrawal studies show that there is a clear tendency for the weight to rebound after withdrawal from semaglutide use, therefore it's very hard to argue that it is the weight / fat mass alone blocking patients from indulging in a healthier lifestyle.

Semaglutide may help manage sustained weight loss by e.g. reducing the effect of reduced leptin baseline, however overall I remain highly skeptical of possibility for semaglutides to be "a first-choice approach to robust weight loss".

[Daishiman]

That has nothing to do with GLP-1 agonists and everything to do with the fact that rapid weight loss without exercise and sufficient protein intake leads to substantial lean mass reduction.

It's still better unless you were woefully weak, in which case a doctor should have prescribed adequate nutrition and physical activity.