Cardiovascular effects of GLP-1 receptor agonists: atherosclerotic outcomes, obesity, HFpEF, and kidney disease — a narrative review.

Abstract

Introduction and Objective. Cardiovascular disease (CVD) is a major cause of morbidity and mortality, especially in type 2 diabetes mellitus (T2DM). Selected glucagon-like peptide-1 receptor agonists (GLP-1RAs) provide cardiovascular benefit beyond glucose lowering. The aim of the review is to summarize compound-specific cardiovascular evidence and data in obesity, heart failure with preserved ejection fraction (HFpEF), and chronic kidney disease (CKD). Review Methods. A narrative review used PubMed, Scopus, and supplementary Google Scholar searches from database inception to 6 August 2026, with reference to SANRA. Landmark cardiovascular outcome trials (CVOTs), randomized trials, meta-analyses, guidelines, and selected mechanistic studies were included. Thirty-two publications were analyzed. Brief description of the state of knowledge. CVOTs show heterogeneous results across GLP-1RAs, ranging from cardiovascular safety to reductions in major adverse cardiovascular events (MACE). SELECT demonstrated secondary-prevention benefit with semaglutide 2.4 mg in adults with overweight or obesity, without diabetes, but with established cardiovascular disease. In obesity-related HFpEF, semaglutide improved symptoms, physical function, and body weight, while effects on mortality and heart-failure hospitalization remain uncertain. Kidney benefits are supported by pooled analyses and FLOW. Gastrointestinal and biliary adverse effects remain relevant safety considerations. Summary. GLP-1RAs reduce cardiovascular risk in selected patients with T2DM, but effects are not uniform across the class. Evidence beyond T2DM remains compound-and population-specific, and further studies should clarify long-term safety, hard heart-failure outcomes, comparative effectiveness, and optimal patient selection.