Abstract
BACKGROUND
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown cardiovascular benefits beyond their established role in treating type 2 diabetes mellitus (T2DM). This review evaluates recent clinical evidence, potential mechanisms, and the expanding use of GLP-1-based therapies in cardiovascular disease.
METHODS
We reviewed major randomized clinical trials assessing cardiovascular, kidney, and heart failure outcomes, along with related mechanistic studies and clinical guidelines published through July 2026.
RESULTS
Early trials, including LEADER, SUSTAIN-6, and REWIND, reported 12%-26% reductions in major adverse cardiovascular events (MACE) in patients with T2DM. More recent trials have extended these findings to other populations. SELECT showed a 20% reduction in MACE among individuals with obesity and established cardiovascular disease but without diabetes, while FLOW demonstrated a 24% reduction in its primary kidney composite outcome. SOUL reported a 14% reduction in MACE with oral semaglutide, and SUMMIT showed a 38% reduction in cardiovascular death or worsening heart failure with tirzepatide. SURPASS-CVOT found tirzepatide to be noninferior, but not superior, to dulaglutide for MACE. These benefits likely involve several mechanisms beyond glucose lowering and weight loss, although gastrointestinal adverse effects still remain a concern.
CONCLUSIONS
Growing clinical evidence supports the use of GLP-1-based therapies beyond diabetes management, particularly in patients with cardiovascular disease, chronic kidney disease, or obesity-related heart failure. Further studies will be needed to understand their mechanisms better, long-term safety, and optimal use in clinical practice.