My reason for being on this is cardiovascular rather than cosmetic, which puts me in a small minority in most of these threads.
Relative versus absolute is the distinction that gets lost: a 20% relative reduction on a high baseline risk is a large absolute benefit, and the same relative figure on a low baseline risk is a small one.
The narrow version of the question is how much of the SELECT benefit is plausibly independent of the weight loss, and whether that distinction changes anything practical.
Numbers rather than impressions, if you have them.
NurseLeah_Nash said:My reason for being on this is cardiovascular rather than cosmetic, which puts me in a small minority in most of these threads.
Mendelian randomization evidence supporting GLP-1 pathway modulation for cardiovascular risk: genetic variants in the GLP1R gene region associated with lower BMI also show associations with reduced cardiovascular risk, confirming a causal pathway[1].
This "natural experiment" (people born with genetically higher GLP-1 signaling being leaner and healthier) provides orthogonal evidence supporting the pharmacological approach. When genetic epidemiology, clinical trials, and mechanistic studies all converge, confidence in the therapeutic approach is high.
[1] Zheng SL, et al. Lancet Diabetes Endocrinol. 2023;11(12):869-879.
anders_CPH said:Mendelian randomization evidence supporting GLP-1 pathway modulation for cardiovascular risk: genetic variants in the GLP1R gene region associated…
Cardiac biomarkers and cardiovascular risk: my cardiologist ordered advanced cardiac labs given my family history. Results were encouraging:
- NT-proBNP: 66 pg/mL (normal, cardiac function preserved)
- Lp(a): 46 nmol/L (genetic, unchanged — expected)
- ApoB: dropped from 141 to 91 mg/dL (excellent response)
- Coronary calcium score: 0 (unchanged from baseline — reassuring)
The ApoB reduction is particularly meaningful — it's considered the best single predictor of cardiovascular risk. GLP-1 therapy seems to improve this consistently.
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Browse GL BiochemNurseLeah_Nash said:My reason for being on this is cardiovascular rather than cosmetic, which puts me in a small minority in most of these threads.
This matches mine closely enough to be worth saying so out loud. I had assumed I was the exception until I read this.
Clinical perspective, offered as context rather than as advice.
NurseLeah_Nash said:...we don't know the long-term effects of cardiovascular risk...
This is a fair point, and I think intellectual honesty requires acknowledging it. GLP-1 agonists in their current form have ~8-10 years of human exposure data. That's not nothing, but it's not 30+ years either.
However: the risk-benefit calculation should also consider the KNOWN long-term effects of untreated obesity — diabetes, cardiovascular disease, cancer, joint destruction, reduced lifespan by 5-10 years.
Uncertainty about GLP-1 long-term safety vs certainty about obesity consequences. The calculus seems clear to me, but reasonable people can disagree.