Prespecified SELECT Analysis Finds Semaglutide Lowered Inflammation Marker Tied to Cardiovascular Risk

Circulation published a prespecified secondary analysis of the SELECT cardiovascular outcomes trial on August 18, 2026, examining the relationship between semaglutide, weight loss, and high-sensitivity C-reactive protein (hsCRP), a blood marker of systemic inflammation. SELECT enrolled 17,604 adults with overweight or obesity and established atherosclerotic cardiovascular disease but not diabetes, and previously reported that semaglutide reduced major adverse cardiovascular events (MACE) compared with placebo over a mean follow-up of 39.8 months. The new analysis was funded by Novo Nordisk, which manufactures semaglutide and markets it as Wegovy.

Baseline hsCRP was similar between the semaglutide group (geometric mean 1.96 mg/L) and the placebo group (geometric mean 1.91 mg/L), and was prognostic of future cardiovascular events: risk of MACE rose across subgroups with baseline hsCRP under 2, 2 to under 10, and 10 mg/L or higher, including significant associations with cardiovascular death and all-cause death. Researchers tracked hsCRP changes and their relationship to time to first MACE, body weight, and other measures over 104 to 208 weeks using Cox modeling and related statistical approaches.

Semaglutide lowered hsCRP by 37.8% at 104 weeks relative to placebo, and reduced MACE risk across every baseline hsCRP subgroup. Larger hsCRP reductions were associated with greater weight loss, but the inflammation changes were evident by weeks 4 and 8, before most weight loss had occurred, and were also observed among participants who did not lose significant weight. The hsCRP changes were independent of LDL cholesterol levels, statin use, and the cardiovascular disease criteria used to enroll participants. The trial is registered with ClinicalTrials.gov as NCT03574597 and is listed as completed.

The authors conclude that hsCRP data, both at baseline and in response to treatment, support inflammation as a prognostic factor for cardiovascular risk in this population, and that the reduction in inflammation may have partially contributed to the MACE benefit semaglutide showed in the main SELECT results. Several authors are Novo Nordisk employees. Semaglutide is already approved by the FDA and the European Medicines Agency and registered with Australia's Therapeutic Goods Administration, marketed as Wegovy for chronic weight management and cardiovascular risk reduction and as Ozempic and Rybelsus for type 2 diabetes. This analysis does not change that regulatory status in any market. It reports associations observed in a prespecified analysis of trial data, not a controlled test of an inflammation-targeted treatment, and is not treatment or dosing guidance; cardiovascular risk management decisions should be made with a qualified clinician.