PharmD_Rodriguez said:Dr.AddMedPHL said: ...cardiovascular risk is just another fad...
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.
InsuranceTom said:Positive "side effect" of cardiovascular risk: my blood pressure dropped so much that I'm now off metoprolol entirely!
Saving this. It is the first explanation that did not require me to already understand it.
PharmD_Rodriguez said:Dr.AddMedPHL said: ...cardiovascular risk is just another fad...
CRP reduction on cardiovascular risk — this is the lab result that excites me most:
Baseline hsCRP: 6.0 mg/L (high cardiovascular risk)
Month 6 hsCRP: 2.5 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 13% to 5%. My cardiologist is genuinely impressed.
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View ResultsBethLabQueen said:My reason for being on this is cardiovascular rather than cosmetic, which puts me in a small minority in most of these threads.
I want to bring up the cardiovascular angle on cardiovascular risk.
The SELECT trial demonstrated a 20% reduction in MACE with semaglutide 2.4mg[1]. This is practice-changing because the CV benefit appears to be independent of the degree of weight loss — suggesting direct vascular and anti-inflammatory mechanisms.
For cardiovascular risk, this means we need to think beyond the primary outcome and consider the cardiovascular implications. The all-cause mortality reduction (HR 0.81) is the most clinically meaningful signal.
[1] Lincoff AM, et al. N Engl J Med. 2023;389(24):2221-2232.
Moderator note: good thread. Keeping it here rather than moving it, because the question is general enough to be useful. Tagging this one for the weekly digest.