Prescribed on cardiovascular grounds rather than for weight, and almost everything written for patients assumes the opposite.
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.
So the question, as narrowly as I can put it: how much of the SELECT benefit is plausibly independent of the weight loss, and whether that distinction changes anything practical.
If the honest answer is that nobody knows, that is a useful answer and I would rather have it.
Dr.ObesityMed 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.
Dr.SleepRoch said:Mendelian randomization evidence supporting GLP-1 pathway modulation for cardiovascular risk: genetic variants in the GLP1R gene region associated…
Metabolic syndrome resolution on cardiovascular risk: I went from meeting 4 of 5 diagnostic criteria to meeting ZERO after 12 months of treatment.
The 5 criteria (and my journey):
- Waist circumference: 51" → 37" ✅ Resolved
- Triglycerides: 247 → 107 ✅ Resolved
- HDL: 35 → 59 ✅ Resolved
- Blood pressure: 147/93 → 120/74 ✅ Resolved
- Fasting glucose: 127 → 87 ✅ Resolved
Metabolic syndrome reversal is, in my view, the most medically significant outcome of GLP-1 therapy.
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View ResultsDr.ObesityMed said:Prescribed on cardiovascular grounds rather than for weight, and almost everything written for patients assumes the opposite.
This matches mine closely enough to be worth saying so out loud. Posting only so the count is not one.
From the other side of the consultation, briefly.
Dizziness and cardiovascular risk: I was lightheaded for the first 2 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.