(P105) SEMAGLUTIDE, INFLAMMATORY MARKERS AND CARDIOVASCULAR OUTCOMES IN PATIENTS WITH OVERWEIGHT OR OBESITY IN THE SELECT TRIAL

Saturday, October 26, 2024

12:00 PM – 12:30 PM PT

Location: BOARD 12

Presenting Author(s)

Amritanshu Shekhar Pandey, ON (he/him/his)

Department of Medicine
McMaster University, Hamilton and Cambridge Cardiac Care, Cambridge, Ontario
Cambridge, Ontario, Canada

First Author(s)

JP

Jorge Plutzky, n/a

Department of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School,
Boston, Massachusetts, United States

Co-Author(s)

PB

Paweł Bogdański, n/a

Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics
Poznan, Wielkopolskie, Poland
SD

Selcuk Dagdelen, n/a

Department of Endocrinology and Metabolism
Ankara, Ankara, Turkey
JD

John E. Deanfield, n/a

Institute of Cardiovascular Sciences,
University College London, London, UK
London, England, United Kingdom
SE

Scott S. Emerson, n/a

Department of Biostatistics
University of Washington, Seattle, WA
Seattle, Washington, United States
GH

G Kees Hovingh, n/a

Novo Nordisk A/S
Søborg, Denmark
Søborg, Hovedstaden, Denmark
SK

Stewven E. Kahn, n/a

Department of Medicine, VA Puget Sound Health Care System
and University of Washington, Seattle, WA
Seattle, Washington, United States
SH

Signe H. Larsen, n/a

Medical & Science 2 CKAD
Søborg, Nordjylland, Denmark
GL

Gustavs Latkovskis, n/a

Institute of Cardiology and Regenerative Medicine
Riga, Baltinavas, Latvia
ML

Michael Lehrke, n/a

Department of Internal Medicine I
Aachen, Nordrhein-Westfalen, Germany
SH

Søren Hardt-Lindenberg, n/a

Novo Nordisk A/S,
Søborg, Denmark
Søborg, Hovedstaden, Denmark
IL

Ildiko Lingvay, n/a

Department of Internal Medicine/Endocrinology
and Peter O’Donnel Jr School of Public Health, UT Southwestern Medical Center, Dallas, TX
Dallas, Texas, United States
SN

Stephen J. Nicholls, n/a

Professor of Cardiology
Clayton, Victoria, Australia
TO

Tugce K. Oral, n/a

Novo Nordisk A/S,
Søborg, Denmark
Søborg, Hovedstaden, Denmark
PP

Paula Perez Terns, n/a

Medical Management, Cardiology Palermo
Buenos, Buenos Aires, Argentina
SR

Søren Rasmussen, n/a

Novo Nordisk A/S,
Søborg, Denmark
Søborg, Hovedstaden, Denmark

Senior Author(s)

PM

Paul M. Ridker, n/a

Director
Canadian Society of Cardiovascular Nuclear and CT Imaging
Boston, Massachusetts, United States
DR

Donna H. Ryan, n/a

Pennington Biomedical Research Center, Baton Rouge, LA
Baton Rouge,, Louisiana, United States
AM

Abraham Michael Lincoff, n/a

Department of Cardiovascular Medicine
Cleveland Clinic, Cleveland Clinic Lerner College of Medicine
Cleveland, Ohio, United States

Disclosure(s):

Amritanshu Shekhar Pandey, ON: No financial relationships to disclose

Background: In SELECT, among 17,604 people with overweight/obesity and cardiovascular (CV) disease but not type 2 diabetes (T2D), weekly subcutaneous semaglutide 2.4 mg significantly reduced major adverse cardiovascular events (MACE) versus placebo. Given the relationship between inflammation, obesity and atherosclerotic complications, we investigated whether inflammatory markers were prognostic of CVD risk in SELECT, and the relationship between treatment with semaglutide and changes in inflammatory markers, weight, and MACE.

METHODS AND RESULTS: We analyzed baseline levels of high-sensitivity C-reactive protein (hsCRP) for predicting CV risk, and the relationship between hsCRP and time to first MACE, baseline weight, weight loss and other clinical parameters among semaglutide vs placebo groups in SELECT. Baseline hsCRP was similar for the semaglutide (median 1.87 mg/L) and placebo (median 1.80 mg/L) groups. Semaglutide reduced hsCRP significantly (37.8%, 104 weeks) vs placebo. Higher values in baseline hsCRP subgroups ( < 2, 2– < 10, ≥10 mg/L) were prognostic of increased MACE risk; semaglutide reduced CV risk as compared with placebo (Figure 1). Greater weight loss was associated with larger hsCRP reductions in the semaglutide and placebo groups (Figure 2). The effects of semaglutide on hsCRP and MACE, which occurred early in the trial, were independent of low-density lipoprotein cholesterol levels, statin use, and CVD entry criteria.

Conclusion: Among people with overweight/obesity and CVD without T2D enrolled in SELECT, baseline hsCRP was a prognostic biomarker for MACE, while greater weight loss was associated with greater hsCRP reduction. Semaglutide significantly reduced MACE across all baseline hsCRP and clinical subgroups.