Prescribed on cardiovascular grounds rather than for weight, and almost everything written for patients assumes the opposite.
What I actually want to know is how much of the SELECT benefit is plausibly independent of the weight loss, and whether that distinction changes anything practical.
Tell me what I have not thought of.
PharmacoVig_BOS said:Prescribed on cardiovascular grounds rather than for weight, and almost everything written for patients assumes the opposite.
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.
MikeFit_NJ said:Mendelian randomization evidence supporting GLP-1 pathway modulation for cardiovascular risk: genetic variants in the GLP1R gene region associated…
NNT calculation for cardiovascular risk clinical endpoints: NNT = 1/ARR (absolute risk reduction).
From SELECT trial: MACE at 39 months — 6.5% semaglutide vs 8.0% placebo. ARR = 1.5%. NNT = 67 over 3.3 years.
Compare to established therapies:
| Intervention | NNT | Timeframe |
|---|---|---|
| Semaglutide (MACE) | 67 | 3.3 years |
| Statins primary prevention (MI) | ~100 | 5 years |
| Aspirin secondary prevention | ~77 | 2 years |
These NNTs are clinically meaningful and comparable to accepted cardiovascular interventions.
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View ResultsPharmacoVig_BOS said:Prescribed on cardiovascular grounds rather than for weight, and almost everything written for patients assumes the opposite.
Can confirm. Same sequence, different timescale. The detail I would add is minor and it is already implied above.
From the other side of the consultation, briefly.
Dizziness and cardiovascular risk: I was lightheaded for the first 3 weeks. Root cause was a combination of reduced caloric intake and mild dehydration.
Fix: minimum 80-100oz water daily, don't skip meals even if you're not hungry (eat small protein-rich snacks), and stand up slowly from sitting/lying positions. Also check your blood pressure — GLP-1-induced weight loss can make BP meds too strong, requiring dose reduction.