InsuranceTom said:SUSTAIN-6 was the first CVOT to show cardiovascular benefit with semaglutide, relevant to cardiovascular risk.
Pushing back on InsuranceTom here. 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.
NeuroNate said:Prescribed on cardiovascular grounds rather than for weight, and almost everything written for patients assumes the opposite.
Anti-inflammatory mechanisms of GLP-1 agonists and cardiovascular risk: beyond weight loss, GLP-1R activation directly suppresses NF-κB signaling, reduces NLRP3 inflammasome activation, and decreases monocyte/macrophage adhesion to endothelium[1].
Clinical correlates: hsCRP reduction of 30-60% (consistently seen across trials), reduced carotid intima-media thickness, and decreased coronary plaque inflammation on PET imaging.
These anti-inflammatory effects likely contribute to the cardiovascular benefit seen in SELECT — and may explain benefits beyond what weight loss alone would predict.
[1] Hogan AE, et al. Diabetologia. 2014;57(4):781-784.
mike_nyc 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" → 37" ✅ Resolved
- Triglycerides: 255 → 110 ✅ Resolved
- HDL: 37 → 57 ✅ Resolved
- Blood pressure: 145/93 → 118/72 ✅ Resolved
- Fasting glucose: 120 → 89 ✅ Resolved
Metabolic syndrome reversal is, in my view, the most medically significant outcome of GLP-1 therapy.
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View ResultsDr.SportsMedIN said:Metabolic syndrome resolution on cardiovascular risk: I went from meeting 3 of 5 diagnostic criteria to meeting ZERO after 14 months of treatment.
Continuous metabolic monitoring dashboard for cardiovascular risk — I track everything in a spreadsheet and here's the month-over-month trend for my key markers:
Weight: consistent downtrend, -1.9 lbs/week average
Fasting glucose (finger stick): stable at 82 mg/dL
Blood pressure (home): 119/72 average
Resting heart rate: 62 bpm (down from 78)
Waist circumference: down 12 inches total
The resting heart rate improvement correlates with cardiovascular fitness gains. Everything is moving in the right direction.