Journal Article Ahead of print 2 citations
PubMed: 42610271 DOI: 10.1161/CIRCULATIONAHA.125.074482
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
Authors: Jorge Plutzky, Paweł Bogdański, Helen M Colhoun, Selcuk Dagdelen, John E Deanfield, Scott S Emerson, G Kees Hovingh, Steven E Kahn, Kathrine Ekström, Gustavs Latkovskis, Michael Lehrke, Søren Hardt-Lindberg, Ildiko Lingvay, Stephen J Nicholls, Tugce Kalayci Oral, Paula P Terns, Søren Rasmussen, Paul M Ridker, Donna H Ryan, A Michael Lincoff
Affiliations
- Division of Cardiovascular Medicine (J.P.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
- Department of Treatment of Obesity, Metabolic Disorders, and Clinical Dietetics, Poznan University of Medical Sciences, Poland (P.B.).
- Institute of Genetics and Cancer, University of Edinburgh, Scotland (H.M.C.).
- Department of Endocrinology and Metabolism, School of Medicine, Hacettepe University, Ankara, Turkey (S.D.).
- Institute of Cardiovascular Sciences, University College London, UK (J.E.D.).
- Department of Biostatistics, University of Washington, Seattle (S.S.E.).
- Novo Nordisk A/S, Søborg, Denmark (G.K.H. K.E. S.H.-L. T.K.O. S.R.).
- Department of Vascular Medicine, Amsterdam University Medical Center, the Netherlands (G.K.H.).
- Department of Medicine, VA Puget Sound Health Care System and University of Washington, Seattle (S.E.K.).
- Faculty of Medicine and Life Sciences, University of Latvia, Riga (G.L.).
- Department of Internal Medicine I, University Hospital Aachen, RWTH Aachen University, Germany (M.L.).
- Department of Internal Medicine/Endocrinology and Peter O'Donnell Jr School of Public Health, UT Southwestern Medical Center, Dallas, TX (I.L.).
- Victorian Heart Institute, Monash University, Clayton, Victoria, Australia (S.J.N.).
- Dirección Médica, Cardiología Palermo-Centro de Investigaciones Clínicas, Buenos Aires, Argentina (P.P.T.).
- Center for Cardiovascular Disease Prevention and Cardiovascular Division (P.M.R.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
- Pennington Biomedical Research Center, Baton Rouge, LA (D.H.R.).
- Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH (A.M.L.).
Abstract
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.
MeSH
Diabetes Mellitus, C-Reactive Protein, Cardiovascular Diseases, Cardiovascular System, Biomarkers, Obesity, Weight Loss, Atherosclerosis, Therapeutics, Overweight, Blood Circulation, Semaglutide