My reason for being on this is cardiovascular rather than cosmetic, which puts me in a small minority in most of these threads.
The narrow version of the question is how much of the SELECT benefit is plausibly independent of the weight loss, and whether that distinction changes anything practical.
Numbers rather than impressions, if you have them.
Dr.KarenChen 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.
amsterdam_pete said:I want to bring up the cardiovascular angle on cardiovascular risk.
Positive "side effect" of cardiovascular risk: my blood pressure dropped so much that I'm now off metoprolol entirely! My cardiologist is thrilled.
If you're on BP meds and losing weight on a GLP-1, monitor your BP at home regularly. Hypotension symptoms (dizziness, lightheadedness when standing) mean your BP meds may need reduction. Don't wait for your next scheduled appointment — call your doctor.
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Browse GL BiochemDr.KarenChen said:My reason for being on this is cardiovascular rather than cosmetic, which puts me in a small minority in most of these threads.
Second this.
Adding the clinical framing, because it changes how the question reads.
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.