LabKate said:

Dizziness and cardiovascular risk: I was lightheaded for the first 2 weeks.

This is where I part company with the consensus forming above. 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.

Correct me if the detail matters more than I have assumed.

Dr.LipidDallas said:

Prescribed on cardiovascular grounds rather than for weight, and almost everything written for patients assumes the opposite.

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.

mike.trainer_LA said:

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

I'm 55 years old and want to share my perspective on cardiovascular risk as an older member of this community.

My doctor was initially hesitant because of my age, but the SELECT trial included patients up to 72 and showed consistent benefit across age groups. We started at the lowest dose with closer monitoring.

8 months later: down 45 lbs, off metoprolol, A1C from 7.0% to 5.2%. My cardiologist is thrilled. cardiovascular risk is absolutely relevant for older adults — don't let anyone tell you otherwise.

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

Did your prescriber agree with that reading, and if not what was their objection?

LindaRN_retired said:

I'm 55 years old and want to share my perspective on cardiovascular risk as an older member of this community.

Anti-inflammatory mechanisms of GLP-1 agonists and cardiovascular risk: beyond weight loss, GLP-1R activation directly suppresses NF-κB signaling, reduces NLRP3 inflammasome activation, and decreases monocyte/macrophage adhesion to endothelium[1].

Clinical correlates: hsCRP reduction of 30-60% (consistently seen across trials), reduced carotid intima-media thickness, and decreased coronary plaque inflammation on PET imaging.

These anti-inflammatory effects likely contribute to the cardiovascular benefit seen in SELECT — and may explain benefits beyond what weight loss alone would predict.