Semaglutide cardiovascular benefit: SELECT trial deep dive — looking for input

TinaHashiRN said:

Senior perspective on cardiovascular risk: I'm 70 years old and started this journey skeptically.

There is a second half to this that has not been said yet. Steady state is the thing most people miss. The terminal half-life is about a week, so every dose step takes four to five weeks to fully express itself. Judging a step at day ten is judging the ascent, not the plateau, and it is the single commonest reason people escalate before they needed to.

OP back with an update, since a thread like this is useless without one.

Update. I did go to 2.4mg in the end, and the honest report is that it bought me less than the step before it and cost me two bad weeks. Worth knowing rather than worth repeating.

One thing that is still open after TinaHashiRN’s answer:

What would you measure differently if you were starting again?

MaxMetOK said:

I did go to 2.4mg in the end, and the honest report is that it bought me less than the step before it and cost me two bad weeks.

CRP reduction on cardiovascular risk — this is the lab result that excites me most:

Baseline hsCRP: 11.0 mg/L (high cardiovascular risk)
Month 6 hsCRP: 3.5 mg/L (moderate risk)
Month 12 hsCRP: 0.4 mg/L (low risk)

This level of inflammatory marker reduction is comparable to what you'd see with statin therapy. Combined with the weight loss, my 10-year ASCVD risk score dropped from 18% to 6%. My cardiologist is genuinely impressed.

MaxMetOK said:

I did go to 2.4mg in the end, and the honest report is that it bought me less than the step before it and cost me two bad weeks.

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.