Beyond weight loss: what SELECT actually established

The evidence

SELECT randomized 17,604 adults aged at least 45 with established cardiovascular disease, BMI of at least 27, and no history of diabetes. The primary composite of cardiovascular death, nonfatal heart attack or nonfatal stroke occurred in 6.5% of semaglutide participants and 8.0% of placebo participants; hazard ratio 0.80 (95% CI 0.72–0.90). Mean follow-up was 39.8 months. The trial was funded by Novo Nordisk.

The trade-off and the boundary

Adverse events led to permanent treatment discontinuation in 16.6% versus 8.2%. This was secondary prevention: the trial did not establish cardiovascular benefit in people without previous atherosclerotic disease. The result also does not establish an equivalent effect for every peptide or every GLP-1 product.

Our interpretation

Editorial interpretation

The editorial lesson is to read the population and the outcome before the headline. A meaningful clinical endpoint deserves different treatment from a laboratory signal or a change in body weight. We will report relative effects alongside event rates and will flag when the evidence applies to a narrow population.