RCT · 2023
Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT)
Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. · New England Journal of Medicine
17,604 participants over a mean 39.8 months showed a 20% relative reduction in major adverse cardiovascular events — the first hard-outcome proof that a weight-loss peptide reduces cardiovascular death.
Key findings
- MACE: 6.5% treated vs 8.0% placebo (HR 0.80)
- Benefit appeared before maximal weight loss, suggesting weight-independent mechanisms
- All-cause mortality trended lower
Limitations
Enrolled participants had established cardiovascular disease; generalizability to primary prevention is unproven.