Effects of GLP-1 receptor agonists on body weight and cardiovascular outcomes: a review

Abstract

Obesity is a rapidly increasing global health challenge that is strongly linked to the cardiorenometabolic syndrome, cardiovascular morbidity, and mortality. Lifestyle interventions remain the cornerstone of treatment, but average long-term weight loss is modest and durable weight maintenance is often limited. Bariatric surgery is not suitable for all patients, and substantial weight regain occurs in a considerable proportion over time. Glucagon-like peptide‑1 receptor agonists (GLP-1RAs), originally developed for type 2 diabetes (T2D), have emerged as potent agents for weight reduction and cardiometabolic risk improvement. By enhancing glucose-dependent insulin secretion, suppressing appetite, improving lipid metabolism, and exerting anti-inflammatory, endothelial, and haemodynamic effects, GLP-1RAs influence multiple pathways relevant to cardiovascular disease. Across large cardiovascular-outcome trials, GLP-1RAs consistently reduce major adverse cardiovascular events (MACE), all-cause mortality, and heart-failure hospitalizations in individuals with T2D. In populations with overweight or obesity without diabetes, semaglutide, as shown in the SELECT trial, has demonstrated significant cardiovascular risk reduction, partly independent of weight loss. Overall, GLP-1RAs represent a therapeutic option for cardiovascular prevention across a broad spectrum of patients at high-risk for or with established CVD. This review provides a comprehensive overview of the pleiotropic cardiovascular effects associated with GLP-1RAs and discusses their potential integration into cardiovascular care.