I'm not diabetic. Can I still benefit from semaglutide for cardiovascular protection?

The SELECT trial was specifically designed for non-diabetic patients (with established CVD and BMI above 27), so yes, the cardiovascular benefit has been proven in non-diabetic patients. This was the specific question SELECT was built to answer, and the answer is affirmative. Prior GLP-1 trials (LEADER, SUSTAIN-6) enrolled patients with type 2 diabetes, raising the question of whether the benefit was diabetes-specific. SELECT removed that ambiguity.

The important qualifier: SELECT enrolled patients with established cardiovascular disease. The extension to primary prevention, non-diabetic men who are overweight and at cardiovascular risk but have not yet had a cardiac event, is a reasonable extrapolation but has not been proven in its own dedicated RCT. This distinction belongs on the Honesty Scale. For post-MI or post-stent patients: Solid (1) evidence. For primary prevention in non-diabetic men: Promising (2), biologically plausible, trial-pending. The risk-benefit calculation is different for these two groups. (Lincoff et al., NEJM, 2023)

Cardiologist's calibrated position, Solid (1) for non-diabetic patients with established CVD and BMI above 27. Promising (2) for primary prevention in non-diabetic patients without established CVD.

What to do: Know which group you are in before the clinical conversation. The evidence base supporting the recommendation is different depending on whether you have had a prior cardiac event.

For the full picture, read The Drug That Surprised Cardiologists.