Adiposopathy-Based Chronic Diseases and Therapeutic Role of Semaglutide

Obesity is increasingly recognized not merely as excess body weight but as adiposity-based chronic disease (ABCD), in which adipose tissue amount, distribution, and dysfunction drive multisystem complications. This review examines the pathophysiological basis of ABCD and positions semaglutide within a complication-centric therapeutic framework extending beyond Body mass index (BMI)-defined obesity. Dysfunctional adiposity contributes to insulin resistance, type 2 diabetes, atherosclerotic cardiovascular (CV) disease, heart failure with preserved ejection fraction, chronic kidney disease, metabolic dysfunction-associated steatotic liver disease/metabolic dysfunction-associated steatohepatitis, and osteoarthritis (OA). The chapter integrates contemporary obesity and metabolic care frameworks, including European Association for the Study of Obesity and American Association of Clinical Endocrinology/American College of Endocrinology concepts, with emerging complication-centric treatment algorithms. Evidence from STEP 1, STEP 2, STEP 4, SELECT, STEP-heart failure with preserved ejection fraction (HFpEF), FLOW, REMODEL, ESSENCE, and STEP-OA support semaglutide as a high-efficacy intervention with benefits extending from weight reduction and glycemic improvement to CV risk reduction, improvement in HF-related symptoms, renal protection, metabolic dysfunction-associated steatohepatitis (MASH) resolution, fibrosis-related benefit, and improvement in OA-related pain and function. Collectively, the review supports a shift from BMI-centric obesity care toward assessment of visceral adiposity and complication burden, with semaglutide positioned as an important therapeutic option for long-term, multisystem management of ABCD