Effect of Semaglutide on MACE Risk Reduction Only Partly Explained by Known Risk Factors

WEDNESDAY, Sept. 30, 2026 (HealthDay News) — The effects of semaglutide on major adverse cardiovascular events (MACE) is only partially due to known risk factors, according to a study published online Sept. 23 in the European Heart Journal.

Helen M. Colhoun, M.B., B.Ch., M.D., from the University of Edinburgh in the United Kingdom, and colleagues examined potential mediators of the cardiovascular benefit (MACE risk reduction) of semaglutide in the SELECT trial. Changes from randomization to 24 months were assessed in body weight, waist circumference, plasma high-sensitivity C-reactive protein (hsCRP), glycated hemoglobin (HbA1c), lipids, blood pressure, estimated glomerular filtration rate, and urinary albumin-to-creatinine ratio individually and in combination.

The researchers observed significant improvement in all potential mediators examined with semaglutide. Point estimates for percentage mediation were largest for waist circumference, hsCRP, HbA1c, and body weight examined separately (64.0, 42.1, 29.0, and 19.5 percent, respectively); all had wide confidence intervals. Unreliability of estimates was suggested for body weight and waist circumference, possibly due to a differing relationship between treatment arms for body weight and waist change with MACE. For all potential mediators, joint mediation combined was estimated to be 31.4 percent in a multivariable analysis. The percentage mediation was 46.0 percent when variables other than body weight and waist circumference were considered.

“Whether we combine all risk factors together or look at some subsets of the risk factors, no more than half of the reduction in heart disease could be explained by the changes in these risk factors,” Colhoun said in a statement. “These results suggest that semaglutide should be considered as a cardiovascular disease reduction drug and not just as a weight loss drug.”

Several authors disclosed ties to biopharmaceutical companies, including Novo Nordisk, which manufactures semaglutide and funded the study.

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