Dr.NutriCornell said:

Mendelian randomization evidence supporting GLP-1 pathway modulation for cardiovascular risk: genetic variants in the GLP1R gene region associated…

Pushing back on Dr.NutriCornell 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.

laura_annarbor said:

My reason for being on this is cardiovascular rather than cosmetic, which puts me in a small minority in most of these threads.

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):

1. Waist circumference: 53" → 37" ✅ Resolved
2. Triglycerides: 243 → 103 ✅ Resolved
3. HDL: 37 → 55 ✅ Resolved
4. Blood pressure: 143/97 → 121/75 ✅ Resolved
5. Fasting glucose: 123 → 89 ✅ Resolved

Metabolic syndrome reversal is, in my view, the most medically significant outcome of GLP-1 therapy.

InsuranceTom said:

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

NNT calculation for cardiovascular risk clinical endpoints: NNT = 1/ARR (absolute risk reduction).

From SELECT trial: MACE at 39 months — 6.5% semaglutide vs 8.0% placebo. ARR = 1.5%. NNT = 67 over 3.3 years.

Compare to established therapies:

These NNTs are clinically meaningful and comparable to accepted cardiovascular interventions.

A narrower follow-up, since the general answer is now clear:

How would you tell the difference between that and the alternative explanation?

PharmacoVig_BOS said:

NNT calculation for cardiovascular risk clinical endpoints: NNT = 1/ARR (absolute risk reduction).

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