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Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes

SELECT trial (n=17,604; mean follow-up ~39.8 months): once-weekly semaglutide 2.4 mg reduced the primary composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke versus placebo in adults ≥45 years with BMI ≥27 and established cardiovascular disease but without diabetes.

Design

  • Double-blind RCT; n = 17,604; median follow-up ~39.8 months
  • Population: age ≥45 y, BMI ≥27 kg/m², preexisting CVD, no baseline diabetes
  • Intervention: subcutaneous semaglutide 2.4 mg weekly vs placebo on top of usual care

Primary outcome (ITT)

  • CV death, nonfatal MI, or nonfatal stroke: HR 0.80 (95% CI 0.72–0.90; P < 0.001) favouring semaglutide

Safety / tolerability signal (abstract)

  • Permanent discontinuation for adverse events higher on semaglutide (~16.6% vs ~8.2% placebo)—largely GI symptoms in trial narrative

Evidence hygiene

  • Obesity + prior CVD enrichment trial—not general primary-prevention of all overweight adults.
  • Pair with STEP obesity body-composition trials and FLOW kidney outcomes on the same protocol page—molecule- and indication-specific labels still apply clinically.

Publication

Lincoff AM, Brown-Frandsen K, Colhoun HM, et al.; SELECT Trial Investigators. N Engl J Med. 2023 Dec 14;389(24):2221-2232. PMID 37952131; NCT03574597.

Outcomes

  • All-Cause Mortality Risk
    Events: /
View original paper →