EAS 2024 – In an analysis of SELECT among CVD patients with overweight or obesity, baseline hsCRP was a prognostic biomarker for subsequent MACE. Semaglutide reduced hsCRP levels early in SELECT prior to major weight loss.

This summary is based on the presentation of Jorge Plutzky, MD (Boston, MA, US) at the EAS Congress 2024 – Semaglutide, inflammatory markers and cardiovascular outcomes in patients with overweight or obesity in the SELECT trial.

Introduction and methods

In SELECT, semaglutide reduced the risk of MACE by 20% in patients with overweight or obesity and CVD without T2D compared with placebo. The inflammatory biomarker hsCRP is a predictor of CV risk. This analysis of SELECT examined whether baseline hsCRP is a predictor of MACE events in SELECT, and what the relationship is between changes in hsCRP over the course of SELECT and CV outcomes and changes in body weight.

The SELECT trial was an international, randomized, double-blind, placebo-controlled trial which randomized 17,604 patients with overweight of obesity to subcutaneous semaglutide 2.4 mg once weekly or matching placebo on top of standard of care. Inclusion criterial were age ≥ 45 years, BMI ≥ 27 kg/m² and established CVD (defined as prior MI, stroke or symptomatic PAD). Patients with a history of diabetes were excluded. The mean follow-up was 39.8 months. hsCRP levels were measured at baseline, and up to 104 weeks. Median hsCRP at baseline was 1.87 mg/L in the semaglutide group and 1.80 mg/L in the placebo group.

Main results

• Semaglutide reduced hsCRP levels from baseline to 104 weeks compared with placebo (between-group difference: -38%; 95%CI: -39,6 to -35.9).
• Semaglutide reduce the risk of MACE across all baseline hsCRP subgroups, which included hsCRP clinical cutoff points (<2 mg/L, 2-10 mg/L, >10 mg/L) and hsCRP tertiles.
• Higher hsCRP levels at baseline predicted increased risk of subsequent MACE.
• Patients who achieved greater weight loss changes in SELECT had larger reductions in hsCRP in both the placebo and semaglutide group.
• The effect of semaglutide versus placebo on hsCRP were greater among patients who achieved greater weight loss (estimated treatment ratio’s (ETRs) were 0.81, 0.71, 0.59, and 0.59 in the <5%, 5 to <10%, 10 to <15, and ≥15% body weight change groups, respectively; the overall ETR was 0.62; 95%CI: 0.60-0.64).
• Greater effect of semaglutide on changes in hsCRP were observed in females compared with males (ETR: 0.56; 95%CI: 0.52-0.69 in females; and 0.65: 95%CI: 0.63-0.67 in males; P for interaction<0.0001).
• The effect of semaglutide on hsCRP changes were independent of baseline hsCRP cutoff points and tertiles, LDL-c tertiles, CV eligibility criteria, statin use, BMI, HbA1c, and UCAR.
• Semaglutide’s effect on hsCRP occurred early in the trial prior to major weight loss changes (reduction in hsCRP was ~12% at 4 weeks and ~20% at 8 weeks; reduction in body weight was ~2% at 4 weeks and ~3% at 8 weeks).

Conclusion

In this analysis of the SELECT trial among CVD patients with overweight or obesity but no diabetes, baseline hsCRP was a prognostic biomarker for subsequent MACE. Changes in hsCRP over the course of SELECT were greater in patients who achieved greater weight loss, and the effect was more pronounced in patients receiving semaglutide. Semaglutide reduced hsCRP early in the trial, when weight loss was still modest.

- Our reporting is based on the information provided at the EAS Congress 2024 -