PharmHunterJen said:

SELECT is the trial that changed the framing of this class, because it was an outcome trial rather than a weight trial: about a 20% relative reduction…

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.

PharmHunterJen said:

SELECT is the trial that changed the framing of this class, because it was an outcome trial rather than a weight trial: about a 20% relative reduction…

I read this differently from PharmHunterJen, 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.

DanielChem_CHI said:

The "earlier than weight loss explains" argument is weaker than this thread makes it sound.

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.

TrialNerd_Beth said:

Positive "side effect" of cardiovascular risk: my blood pressure dropped so much that I'm now off metoprolol entirely!

This is my experience too, for whatever a second data point is worth. Posting only so the count is not one.