TrialNerd_Beth said:6 month update on cardiovascular risk: down 57 lbs, off blood pressure meds, A1C normalized.
I read this differently from TrialNerd_Beth, on substance rather than tone. The "earlier than weight loss explains" argument is weaker than this thread makes it sound. Blood pressure and inflammatory markers move fast and are downstream of early weight loss, so the mechanism is not as cleanly separable as the summaries imply.
oliver_london said:Prescribed on cardiovascular grounds rather than for weight, and almost everything written for patients assumes the opposite.
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.
LabKate said:The "earlier than weight loss explains" argument is weaker than this thread makes it sound.
Metabolic syndrome resolution on cardiovascular risk: I went from meeting 3 of 5 diagnostic criteria to meeting ZERO after 14 months of treatment.
The 5 criteria (and my journey):
- Waist circumference: 53" → 35" ✅ Resolved
- Triglycerides: 261 → 101 ✅ Resolved
- HDL: 37 → 53 ✅ Resolved
- Blood pressure: 141/91 → 119/73 ✅ Resolved
- Fasting glucose: 126 → 89 ✅ Resolved
Metabolic syndrome reversal is, in my view, the most medically significant outcome of GLP-1 therapy.
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View ResultsOne thing that is still open after RegAffairsDC’s answer:
Did your prescriber agree with that reading, and if not what was their objection?
PedsEndoPhilly said:Metabolic syndrome resolution on cardiovascular risk: I went from meeting 3 of 5 diagnostic criteria to meeting ZERO after 14 months of treatment.
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.