Incretin-based therapies have changed the management of type 2 diabetes and obesity. Semaglutide acts through the glucagon-like peptide-1 receptor, while tirzepatide combines glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonism. These therapies were initially used mainly for glycaemic control and weight reduction, but recent evidence suggests that their role now extends into obesity-related organ disease, including atherosclerotic cardiovascular disease, heart failure with preserved ejection fraction, chronic kidney disease, metabolic dysfunction-associated steatohepatitis, and obstructive sleep apnoea. This review summarizes evidence for semaglutide and tirzepatide across obesity-related cardiometabolic, renal, and hepatic outcomes, as well as obstructive sleep apnoea-related outcomes. A targeted literature search was conducted using PubMed, MEDLINE, major journal websites, and regulatory sources from database inception to May 16, 2026. Current evidence supports clinically important benefits in selected patients, although the strength of evidence varies by condition. Important limitations include treatment durability, weight regain after discontinuation, adverse effects, peri-procedural considerations, pregnancy avoidance, cost, drug supply, and unequal access. These therapies should therefore be viewed as potential components of chronic disease management for selected patients with obesity, type 2 diabetes, or obesity-related cardiometabolic, renal, hepatic, or sleep-disordered breathing complications, rather than as short-term weight-loss interventions.
