Glucagon-Like Peptide-1 (GLP-1)-Based Therapies and Heart Failure Outcomes: A Scoping Review of Contemporary Randomized Controlled Trials.

Glucagon-like peptide-1 (GLP-1)-based therapies have been observed to produce cardiovascular benefits in cardiometabolic diseases; however, their impact on heart failure-specific outcomes is only becoming known through dedicated randomized controlled trials (RCTs). This scoping review consolidates the most recent randomized data that examine how GLP-1-based therapies affect heart failure-specific symptoms, functional capacity, and the occurrence of clinical events. Literature searches were conducted in PubMed, Google Scholar, and CINAHL for RCTs and prespecified analyses between 2021 and 2026 evaluating GLP-1-based therapies and reporting heart failure-specific outcomes. Five RCT-based studies met inclusion criteria, including randomized trials and prespecified RCT-derived analyses evaluating semaglutide and tirzepatide. Among patients with heart failure with preserved ejection fraction (HFpEF) and obesity, semaglutide significantly improved Kansas City Cardiomyopathy Questionnaire Clinical Summary Score and 6-minute walk distance compared to placebo. Tirzepatide exhibited improvements across symptoms and functional and event-based outcomes, with prespecified trajectory analyses confirming favorable shifts in New York Heart Association functional class, Patient Global Impression of Severity, health-related quality of life, and background heart failure medication use. Among patients with type 2 diabetes mellitus and chronic kidney disease, semaglutide was associated with a significantly reduced rate of cardiovascular death or worsening heart failure events. Although the available evidence comes from a small number of recent randomized and prespecified RCT-based studies, current findings suggest that GLP-1-based therapies are associated with improvements in symptoms and functional capacity and reductions in heart failure events in certain patient populations, especially those with HFpEF and obesity. These beneficial effects support a potential role for the integration of GLP-1-based therapies in population-specific heart failure management.