These types of arguments are somewhat worthless when they're not made in context to obesity.
What I mean is, you should be comparing the risk of GLP-1s versus the risk of obesity, because realistically this is the vast majority of people's risk analysis criteria here.
Obesity increases your risk of CVD, metabolic syndrome, diabetes, liver disease, kidney disease, joint diseases, and overall mortality. CVD, in particular, is the number 1 cause of death in many developed countries.
Like all drugs, GLP-1s come with risk. This fact, however, is worthless. We must ask if it is less risky than the aggregate sum of the above diseases. I think the answer is overwhelming yes.
Therefore, obese people should probably consider GLP-1 medications. Particularly if they have tried, and failed, weight loss before. Which every obese person has.
In addition, when considering the downside of medication, we MUST compare it to the alternatives. Many obese people are already on multiple life-long medications. Statins, hypertension medication, insulin and other diabetes management drugs, etc.
Not only do these medications require significantly more management than a GLP-1, but they, too, come with their own set of risks, which we must then add to the risk of disease.
I, personally, have taken multiple chemotherapy drugs to cure my cancer. These drugs make GLP-1s look like nothing. They have damaged my body in irreversible ways. They've aged my blood, exposed me to extreme levels of known carcinogens, raised my risk of mortality, and overall lowered my quality of life.
However, I am thankful for them. Yes, my risk of mortality is much higher. But, compared to cancer, which has a 100% chance to kill me, it was a worthy tradeoff.
Your citation measures 15-year mortality in adults 20-49. The P values for BMI's relationship with all-cause mortality and cardiac mortality were 0.071 and 0.030 respectively. It compares BMI against waist circumference and body fat percentage and suggests that the latter measures are better. I think it's misleading to say that "weight is not a primary predictor of health" based on this evidence.
First, the paper is talking about BMI rather than weight.
Second, what most people mean by "weight" in ordinary conversation is closer to body fat percentage than it is to BMI: Arnold Schwarzenegger was famously obese by BMI, but anybody who called him overweight during a conversation at the pub would likely be told he doesn't count.
Thirdly, the paper was close to statistical significance, even looking at young people and even with a cohort of a bit under 5000 people, so it doesn't rule out a correlation with BMI either (although yes, it does suggest BMI is a proxy for body fat, but this isn't a controversial statement).
Fourthly, GLP-1 agonists do reduce body fat[0], and body fat is the measure suggested by the paper you cited as being better than BMI.
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.
> 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.
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:
>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.
> 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".
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.
