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Phase 3 RCT (double-blind, placebo-controlled, event-driven cardiovascular outcomes trial) · PMID 37840095

Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT) — VialBase Research

20% reduction in MACE (major adverse cardiovascular events) with semaglutide 2.4mg

Last updated · 2023 · Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. · New England Journal of Medicine
Key findings
  • 20% reduction in MACE (major adverse cardiovascular events) with semaglutide 2.4mg
  • HR 0.80 (95% CI 0.72-0.90, P<0.001)
  • First anti-obesity drug to demonstrate cardiovascular benefit independent of diabetes
  • 17,604 participants with overweight/obesity and established CVD, without diabetes
  • Mean follow-up 39.8 months

Summary

The SELECT trial was a landmark cardiovascular outcomes trial that enrolled 17,604 adults aged ≥45 with BMI ≥27, established cardiovascular disease (prior MI, stroke, or peripheral arterial disease), and without diabetes. Participants received semaglutide 2.4mg or placebo weekly, with a mean follow-up of 39.8 months. The primary endpoint was a composite of cardiovascular death, non-fatal MI, or non-fatal stroke (3-point MACE).

Key Findings

  • Primary endpoint (3P-MACE): HR 0.80 (95% CI 0.72-0.90, P<0.001) — 20% relative risk reduction
  • Cardiovascular death: HR 0.85 (not individually significant)
  • Non-fatal MI: HR 0.72 (significant reduction)
  • Non-fatal stroke: HR 0.93 (not individually significant)
  • All-cause mortality: HR 0.81 (numerically lower but study not powered for this endpoint)
  • Mean weight loss: 9.4% with semaglutide vs 0.9% with placebo
  • Benefits appeared to accrue over time, with curves separating progressively
  • Serious adverse events were balanced between groups

Relevance to Semaglutide

SELECT fundamentally changed the positioning of semaglutide from a weight-loss drug to a cardiometabolic therapeutic. It was the first trial to demonstrate that an anti-obesity medication could reduce cardiovascular events in patients without diabetes — bridging the gap between weight loss and hard clinical outcomes. This led to expanded labeling and positioned semaglutide as relevant to cardiologists, not just endocrinologists and obesity specialists. The trial also provided the strongest evidence that GLP-1 RA cardiovascular benefits extend beyond glucose-lowering effects.

Citation

Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med. 2023;389(24):2221-2232. doi:10.1056/NEJMoa2307563.

See Also

View on PubMed · PMID 37840095 →