Suyog Ishwar Jawale

Background: Type 2 diabetes mellitus and obesity frequently coexist and contribute to cardiovascular and renal complications. Semaglutide, a long-acting glucagon-like peptide-1 receptor agonist, has expanded incretin pharmacology beyond glucose lowering toward broader cardiometabolic therapy. Methods: This narrative review integrated pharmacological and clinical evidence on semaglutide. Priority was given to pivotal randomized controlled trials, cardiovascular and renal outcome trials, pharmacokinetic studies and clinically relevant follow-up studies from the SUSTAIN, PIONEER, STEP, SELECT and FLOW programmes. Results: Semaglutide enhances glucose-dependent insulin secretion, suppresses glucagon, reduces appetite and energy intake, and delays gastric emptying. Once-weekly subcutaneous and once-daily oral formulations produced clinically important reductions in glycated hemoglobin and body weight. Semaglutide reduced major adverse cardiovascular events in high-risk patients with type 2 diabetes, lowered cardiovascular events in patients with established cardiovascular disease and obesity without diabetes, and slowed chronic kidney disease progression in patients with diabetes and chronic kidney disease. Gastrointestinal adverse effects were the main tolerability limitation, and substantial weight regain occurred after treatment withdrawal. Conclusion: Semaglutide is an important cardiometabolic therapy; optimal use requires patient selection, gradual dose escalation, monitoring and long-term treatment planning.