Overview
- The Lancet prespecified analysis of 17,604 adults with overweight or obesity and established cardiovascular disease reported fewer major adverse cardiovascular events with once-weekly semaglutide versus placebo.
- Event curves separated by about 20 weeks of treatment (hazard ratio 0.58 for first events at week 20), indicating an early effect that persisted over long-term follow-up.
- Changes in waist circumference by week 20 explained roughly 33% of the treatment effect, while the amount of weight lost did not mediate risk reduction in the semaglutide arm.
- Benefits were consistent across baseline measures of body habitus, prompting discussion of use beyond strict BMI cutoffs, though such implications remain to be tested.
- Researchers cautioned the post-randomization analyses are exploratory and the predominantly White, male population limits generalizability; week-20 averages showed −6.4% body weight and −5.0 cm waist with semaglutide versus −0.8% and −1.1 cm with placebo.