Semaglutide lowered hsCRP by 38% in SELECT, and the fall came before the weight loss

Design

Prespecified secondary analysis of a randomised, double-blind, placebo-controlled trial (SELECT)

Population

17,604 adults with atherosclerotic cardiovascular disease and overweight or obesity, without diabetes

Primary outcome

hsCRP change and its relation to time to first MACE

Effect

hsCRP −37.8% at 104 weeks with semaglutide; MACE reduced across all baseline hsCRP bands

This is a prespecified secondary analysis of SELECT, which randomised 17,604 adults with established atherosclerotic cardiovascular disease and overweight or obesity, but no diabetes, to semaglutide or placebo for a mean of 39.8 months. The main trial already showed fewer major adverse cardiovascular events (MACE). This analysis asked where inflammation fits.

Baseline hsCRP was similar in both arms (geometric mean about 1.9 to 2.0 mg/L) and predicted MACE, cardiovascular death and all-cause death, with risk rising across the <2, 2 to <10 and ≥10 mg/L bands. Semaglutide lowered hsCRP by 37.8% at 104 weeks and reduced MACE in every hsCRP band. The fall in hsCRP was visible by weeks 4 and 8, before major weight loss, was seen in people who did not lose weight, and was independent of LDL cholesterol and statin use.

The authors' modelling suggests reduced inflammation contributed in part to the MACE benefit. That supports a mechanism; it does not show that lowering hsCRP by any means would do the same.

In clinic, this strengthens the case that a patient's cardiovascular benefit from semaglutide does not depend solely on how much weight they lose. hsCRP remains a risk marker worth recording in secondary prevention, not a treatment target on its own.

• Do not judge semaglutide's cardiovascular value in a patient with established atherosclerotic disease only by kilograms lost.
• hsCRP of 2 mg/L or more in a well-treated secondary-prevention patient marks higher residual risk and is worth recording.
• The hsCRP fall was independent of LDL cholesterol and statin use, so it is not a substitute for lipid lowering.
• SELECT excluded diabetes; extrapolating the inflammatory finding to type 2 diabetes is reasonable but not directly tested here.

Why it matters

It challenges the assumption that a patient who loses little weight on semaglutide is getting little cardiovascular benefit.

Don't overread it

The link between hsCRP reduction and fewer events is association within a trial arm; it does not make hsCRP a treatment target.

The statistics, in plain English

A 37.8% reduction in hsCRP means the average level fell to about three-fifths of where it started. 'Prognostic' means higher hsCRP went with more events; it does not prove hsCRP causes them. The modelling that attributes part of the benefit to inflammation is an estimate built on associations within the trial, not a separate randomised comparison.

Read the rest in the app

You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.

Get Daily Doctor — free

Scan to keep reading on your phone. No account needed to start.