Semaglutide and cardiovascular risk reduction: a mediation analysis of the SELECT trial
Colhoun HM, Lincoff AM, Ryan D, et al. (2026). European Heart Journal.
Summary
A mediation analysis of the SELECT trial, in which semaglutide reduced major cardiovascular events against placebo in adults with established cardiovascular disease and overweight or obesity, without diabetes. The authors tested how much of that reduction could be explained by two-year changes in body weight, waist circumference, hsCRP (an inflammation marker), HbA1c, lipids, blood pressure and kidney measures. Semaglutide improved all of them. Waist circumference and hsCRP had the largest point estimates, but every estimate had wide confidence intervals, and supplementary analyses suggested the body weight and waist estimates were unreliable. The authors conclude the cardiovascular effect could not be attributed to known risk factors with any certainty.