Lancet

Semaglutide cuts heart risk in people with obesity, even without significant weight loss

October 30, 2025

Semaglutide’s cardioprotective effects are largely independent of baseline adiposity and weight loss, with only modest mediation by waist circumference reduction. These findings support semaglutide’s use for secondary cardiovascular prevention in patients with overweight/obesity, highlighting mechanisms beyond adiposity reduction.

Study details: The SELECT trial (NCT03574597) randomized 17,604 adults (≥45 years; BMI ≥27 kg/m²; established cardiovascular disease, no diabetes) across 41 countries to once-weekly semaglutide 2.4 mg or placebo. This prespecified analysis assessed the relationship between baseline adiposity (weight, waist circumference), treatment-induced changes, and major adverse cardiovascular events (MACE).

Results: Semaglutide significantly reduced MACE incidence compared with placebo, with consistent benefit across all baseline weight and waist circumference categories. Lower baseline bodyweight and waist circumference were associated with lower MACE risk in both groups, but only waist circumference reduction (not weight loss) during treatment correlated with reduced subsequent MACE risk in the semaglutide arm. Mediation analysis estimated that 33% of semaglutide’s MACE benefit was attributable to waist circumference reduction, suggesting additional mechanisms of action.

Source:

Deanfield J, et al. (2025, October 22). Lancet. Semaglutide and cardiovascular outcomes by baseline and changes in adiposity measurements: a prespecified analysis of the SELECT trial. https://pubmed.ncbi.nlm.nih.gov/41138739/