The SELECT Trial, Broken Down

The SELECT trial (NEJM, 2023) randomized 17,604 adults with overweight/obesity and established cardiovascular disease (but no diabetes) to once-weekly semaglutide 2.4 mg or placebo over ~40 months. The primary composite endpoint — cardiovascular death, nonfatal MI, or nonfatal stroke — occurred in 6.5% of the semaglutide group vs 8.0% of placebo: a 20% relative reduction (HR 0.80, P<0.001).

Beyond the headline: participants lost a mean 9.4% of body weight (vs 0.88% placebo), systolic BP fell ~3.3 mm Hg more than placebo, high-sensitivity CRP dropped ~38%, and a pre-specified kidney composite was reduced 22%. This thread walks members through the trial design and what the numbers mean for cardiometabolic risk.