Semaglutide Lowers hsCRP in SELECT Cardiovascular Analysis

A prespecified secondary analysis of SELECT, published in Circulation, found that semaglutide lowered high-sensitivity C-reactive protein (hsCRP). Modeling suggested reduced inflammation may have contributed in part to the observed reduction in major adverse cardiovascular events (MACEs).

The phase 3, randomized, double-blind, placebo-controlled trial was conducted at 804 sites in 41 countries. It enrolled 17,604 adults, ≥45 years of age, with established atherosclerotic cardiovascular disease and overweight or obesity, but without diabetes. Participants received once-weekly semaglutide titrated to 2.4mg or placebo in addition to standard care and were followed for a mean of 39.8 months.

The substudy examined whether baseline hsCRP predicted MACE risk and evaluated relationships between changes in hsCRP, time to first MACE, and body weight over 104 to 208 weeks using approaches including Cox modeling. Geometric mean baseline hsCRP was 1.96mg/L with semaglutide and 1.91mg/L with placebo. MACE risk increased across baseline hsCRP categories of less than 2, 2 to less than 10, and at least 10mg/L, with significant associations also reported for cardiovascular and all-cause death.

At 104 weeks, semaglutide produced a placebo-corrected 37.8% reduction in hsCRP (95% CI, 35.9%-39.7%). Among participants with early measurements, hsCRP declined 12% by week 4 and 19% by week 8, when weight reductions were 1.4% and 2.8%, respectively. Larger hsCRP reductions were associated with greater weight loss, but declines preceded major weight loss and occurred among participants without weight loss. The changes were independent of low-density lipoprotein cholesterol, statin use, and cardiovascular disease entry criteria.

Semaglutide reduced MACE risk across all baseline hsCRP subgroups, and hsCRP reductions were prognostic of decreased MACE risk. The investigators noted that hsCRP is a single inflammatory biomarker and not a pathogenic mediator, and that no specific adjustment was made for multiplicity. Novo Nordisk A/S funded the trial.

Source: Plutzky J, Bogdański P, Colhoun HM, et al. Effect of semaglutide on the inflammatory biomarker high-sensitivity CRP in patients with established cardiovascular disease and overweight or obesity in SELECT: a prespecified secondary analysis. Circulation. Published online August 18, 2026. doi:10.1161/CIRCULATIONAHA.125.074482