Beyond Glycaemic Control: The Expanding Role of GLP-1 Receptor Agonists in Obesity, Obstructive Sleep Apnoea, Cardiovascular Disease, and Steatohepatitis: A Narrative Review

Abstract

Background: Obesity and its associated metabolic complications, including type 2 diabetes mellitus, cardiovascular disease, obstructive sleep apnoea, and steatotic liver disease, represent interconnected clinical challenges driven by overlapping mechanisms such as insulin resistance, adiposity, inflammation, endothelial dysfunction, and altered hepatic metabolism. Glucagon-like peptide-1 receptor agonists were originally developed for glycaemic control, but accumulating evidence suggests broader therapeutic effects across obesity-related multimorbidity. Objective: This narrative review aimed to synthesize contemporary clinical and mechanistic evidence on GLP-1 receptor agonists and related incretin-based therapies beyond glycaemic control, with emphasis on obesity, cardiovascular disease, obstructive sleep apnoea, and metabolic dysfunction-associated steatotic liver disease/metabolic dysfunction-associated steatohepatitis. Methods: A focused narrative synthesis was undertaken using evidence from randomized controlled trials, cardiovascular outcome trials, phase 2 and phase 3 studies, and clinically relevant mechanistic and review literature. Priority was given to human clinical evidence evaluating liraglutide, semaglutide, dulaglutide, tirzepatide, and related incretin-based therapies in obesity-related cardiometabolic, respiratory, and hepatic disease contexts. Findings were organized thematically by disease domain and interpreted according to evidence maturity, agent specificity, clinical relevance, and safety considerations. Results: The strongest evidence supports clinically meaningful weight reduction with liraglutide, semaglutide, and tirzepatide, and cardiovascular risk reduction with selected GLP-1 receptor agonists in high-risk populations. Evidence in obstructive sleep apnoea is emerging, with improvements largely linked to weight reduction, particularly in tirzepatide trials. Hepatic evidence in MASLD/MASH is promising but heterogeneous, with benefits varying by agent, fibrosis stage, and histological endpoint. Gastrointestinal adverse effects remain the most frequent tolerability concern, while long-term safety and durability in non-diabetic populations require continued evaluation. Conclusion: GLP-1 receptor agonists and related incretin-based therapies are increasingly relevant beyond diabetes management, particularly in obesity-centered cardiometabolic care. Their use should be evidence-calibrated, agent-specific, and integrated within multidisciplinary treatment pathways while further research clarifies long-term outcomes, comparative effectiveness, access, and emerging indications