The Semaglutide Effect: Redefining Treatment Across Diabetes, Obesity, and Cardiometabolic Risk

Abstract

Semaglutide, a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist, has become one of the most consequential pharmacologic agents introduced in endocrinology and metabolic medicine in the past decade. Originally developed for glycemic control in type 2 diabetes, semaglutide has since demonstrated substantial efficacy for chronic weight management and a reduction in major adverse cardiovascular events in patients with established cardiovascular disease and overweight or obesity. This review synthesizes current evidence on semaglutide's pharmacology, mechanism of action, and clinical efficacy across diabetes, obesity, and cardiovascular indications, drawing on data from the STEP, SUSTAIN, and SELECT trial programs. Safety considerations, including gastrointestinal, psychiatric, ophthalmologic, and dermatologic/facial adverse effects, are examined alongside practical considerations for nutritional support, weight-loss maintenance, and treatment discontinuation. The review concludes with a discussion of current clinical practice guidelines and unresolved questions that merit further investigation.