Positioning of Semaglutide among Evolving Guidelines in the Management of Obesity and Related Comorbidities

This chapter positions semaglutide within evolving evidence- and guideline-based management of obesity and related comorbidities across obesity/type 2 diabetes, cardiovascular disease/chronic kidney disease, and metabolic dysfunction-associated steatotic liver disease/metabolic dysfunction-associated steatohepatitis (MASH). Obesity is now recognized as a chronic, relapsing adiposity-based disease by the American Medical Association, world obesity federation, American Association of Clinical Endocrinology (AACE), European Association for the Study of Obesity (EASO), Obesity Canada, and other international bodies. In the Indian context, this has particular relevance because of higher visceral adiposity and cardiometabolic risk at lower Body Mass Index thresholds. Across the AACE framework, EASO guidance, the 2024 American Diabetes Association (ADA) Standards of Care, the ADA/European Association for the Study of Diabetes consensus report, European Society of Cardiology chronic coronary syndrome guidance, American College of Cardiology heart failure (HF) pathways, kidney disease chronic kidney disease algorithms, and European Association for the study of the liver-based MASH guidance, semaglutide is consistently positioned as a high-efficacy option when weight reduction, glycemic control, and organ protection are concurrent priorities. Evidence from semaglutide treatment effect in people with obesity (STEP), Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity, STEP-heart failure with preserved ejection fraction (HFpEF), STEP-HFpEF diabetes mellitus, effect of semaglutide versus placebo on the progression of renal impairment in subjects with type 2 diabetes and chronic kidney disease, Researching Mechanisms of Semaglutide in Diabetic Kidney Disease, and ESSENCE supports semaglutide’s benefits on clinically meaningful weight loss, major adverse cardiovascular events, HF–related symptoms and outcomes, kidney endpoints including urinary albumin-to-creatinine ratio and estimated glomerular filtration rate decline, and histologic as well as noninvasive liver outcomes in MASH. Collectively, current guidelines and trial data support semaglutide as a key therapy within a complication-based, risk-based, and long-term management approach to obesity and multisystem cardiometabolic disease.