Related Experiment Videos
Effect of Semaglutide on the Inflammatory Biomarker High-Sensitivity CRP in Patients With Established Cardiovascular
Jorge Plutzky1, Paweł Bogdański2, Helen M Colhoun3
1Division of Cardiovascular Medicine (J.P.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Insights
Semaglutide significantly reduced major adverse cardiovascular events (MACEs) in patients with overweight or obesity. Reductions in high-sensitivity C-reactive protein (hsCRP) levels with semaglutide were associated with decreased MACE risk, suggesting inflammation plays a role.
Area of Science:
- Cardiology
- Endocrinology
- Inflammation Research
Background:
- The SELECT trial investigated semaglutide's effect on cardiovascular events in patients with overweight/obesity and atherosclerotic cardiovascular disease (ASCVD).
- Inflammation, indicated by high-sensitivity C-reactive protein (hsCRP), is a known cardiovascular risk biomarker in obesity and ASCVD.
- The SELECT trial offers a unique opportunity to explore the interplay of hsCRP, weight, and MACEs with semaglutide treatment.
Purpose of the Study:
- To assess if baseline hsCRP levels predict MACE risk in the SELECT trial.
- To examine the relationship between hsCRP changes and MACEs, weight loss, and other clinical factors.
- To investigate the role of inflammation in semaglutide's cardiovascular benefits.
Main Methods:
- A prespecified substudy of the SELECT trial analyzed hsCRP levels.
- Cox modeling was used to evaluate baseline hsCRP as a predictor of MACE risk.
- Relationships between hsCRP changes and clinical outcomes were assessed over 104-208 weeks.
Main Results:
- Baseline hsCRP levels were similar between semaglutide and placebo groups and predicted MACE risk.
- Semaglutide significantly reduced hsCRP levels and MACE risk across all hsCRP subgroups.
- Reductions in hsCRP with semaglutide preceded significant weight loss and were independent of lipid levels and statin use.
Conclusions:
- Elevated baseline hsCRP is a prognostic factor for cardiovascular risk in patients with overweight/obesity and ASCVD.
- Semaglutide treatment led to decreased hsCRP levels, suggesting a reduction in inflammation.
- The cardiovascular benefits of semaglutide in the SELECT trial may be partly attributed to decreased inflammation.
Background:
In SELECT (Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity), among 17 604 patients with known atherosclerotic cardiovascular disease and overweight or obesity, but not diabetes, randomization to the glucagon-like peptide-1 receptor antagonist semaglutide significantly reduced the primary outcome of major adverse cardiovascular events (MACEs; cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) compared with placebo (mean follow-up, 39.8 months). Inflammation, as indicated by plasma hsCRP (high-sensitivity C-reactive protein) level, is implicated as a biomarker predicting cardiovascular risk in obesity and atherosclerotic cardiovascular disease. SELECT provides a unique opportunity to study the relationship among hsCRP, obesity, weight loss, and MACE outcomes in semaglutide versus placebo groups.
Methods:
In this prespecified SELECT substudy, we evaluated whether baseline hsCRP levels predicted MACE risk and examined the relationships between changes in hsCRP levels and time to first MACE, baseline body weight, weight loss, and other clinical measures among treatment groups over time (104-208 weeks) using multiple approaches, including Cox modeling.
Results:
Baseline hsCRP level, which was similar in the semaglutide (geometric mean 1.96 mg/L) and placebo (geometric mean 1.91 mg/L) groups, was prognostic of future MACEs. The risk of MACEs increased across baseline hsCRP level <2, 2-<10, and ≥10 mg/L subgroups, including significant associations with cardiovascular and all-cause death. Semaglutide reduced hsCRP levels (-37.8% [104 weeks]) and risk of MACEs across all hsCRP subgroups. Greater reductions in ratio-to-baseline hsCRP with semaglutide were associated with greater weight loss, but preceded major weight loss, evident by 4 and 8 weeks, and occurred among those without weight loss. Semaglutide-associated changes in hsCRP were independent of low-density lipoprotein cholesterol levels, statin use, and atherosclerotic cardiovascular disease entry criteria. hsCRP reductions were found to be prognostic of decreased risk of MACEs. Modeling suggests decreased inflammation as contributing in part to the benefits seen with semaglutide in SELECT.
Conclusions:
In SELECT, hsCRP data at baseline and in response to treatment with semaglutide support inflammation as a potential prognostic factor associated with cardiovascular risk in these generally well-treated patients with atherosclerotic cardiovascular disease and overweight or obesity but not diabetes. These findings suggest that the MACE reduction observed with semaglutide versus placebo in SELECT may have partially involved a decrease in inflammation.
Registration:
URL: https://clinicaltrials.gov; Unique identifier: NCT03574597.
Related Concept Videos
01:24Glucagon-like Receptor Agonists
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by the...
01:26Oral Hypoglycemic Agents: Biguanides and Glitazones
01:23Dipeptidyl Peptidase 4 Inhibitors