Cardioprotective Effects of Semaglutide Independent of Adiposity

WEDNESDAY, Oct. 29, 2025 (HealthDay News) -- The cardioprotective effects of semaglutide are independent of baseline adiposity and weight loss, according to a study published online Oct. 22 in The Lancet.John Deanfield, M.B., B.Chir., from University College London, and colleagues reported a prespecified analysis of the SELECT trial to examine the relationship between baseline adiposity measures, treatment-induced adiposity changes, and subsequent risk for major adverse cardiovascular events (MACE) among patients aged 45 years or older with a body mass index of at least 27 kg/m2. Participants were randomly assigned to once-weekly semaglutide 2.4 mg or placebo.Among 17,604 patients enrolled in SELECT, semaglutide significantly reduced the incidence of MACE compared with placebo, with consistent benefits across categories of baseline weight and waist circumference. In the semaglutide group, lower baseline body weight and waist circumference were associated with a lower incidence of MACE (hazard ratio, 0.96 per 5 kg lower body weight and per 5 cm smaller waist circumference). Lower baseline waist circumference, but not body weight, was associated with a lower MACE risk in the placebo group; paradoxically, weight loss was associated with increased MACE risk. No linear trend linking weight loss at week 20 to subsequent MACE risk was seen in those receiving semaglutide; lower subsequent MACE risk was seen in association with greater waist circumference reduction at week 20, and lower in-trial risk of MACE was seen with waist circumference reduction by week 104. Waist circumference reduction mediated about 33 percent of the observed benefit."Semaglutide resulted in improved cardiovascular outcomes, independent of baseline adiposity and over a wide range of treatment-induced weight loss," the authors write.Several authors disclosed ties to the biopharmaceutical industry, including Novo Nordisk, which funded the study.Abstract/Full Text.Sign up for our weekly HealthDay newsletter