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SELECT mediation analysis cannot explain semaglutide's 20% MACE reduction

Waist circumference accounted for an estimated 64% and hsCRP 42% of the benefit, but all confidence intervals were wide and joint mediation was uncertain.

By Maren Holt · Senior Reporter, GLP-1

Sep 22 20:00 ETSource: European heart journal

The wire

01In European Heart Journal, authors applied the Vansteelandt repeated regression method to SELECT and found combined mediation of 31.4% (95% CI -30.1 to 143.6) across weight, waist, hsCRP, HbA1c, lipids, blood pressure and renal measures.
02Clinicians cannot attribute semaglutide's cardiovascular benefit in non-diabetic patients with obesity to weight loss or conventional risk-factor change alone.
03Estimates for body weight and waist circumference appeared unreliable; the authors call for investigation of additional biomarkers and mediators.

From the source

Semaglutide and cardiovascular risk reduction: a mediation analysis of the SELECT trial
European heart journal · 2026 Sep 23 · Colhoun HM, Lincoff AM, Ryan D et al.

Read at pubmed.ncbi.nlm.nih.gov

Source URL https://pubmed.ncbi.nlm.nih.gov/42777687/