Adiposity-based Chronic Diseases and the Therapeutic Role of Glucagon-like Peptide-1 Receptor Agonists

Abstract Adiposity-Based Chronic Disease (ABCD) is a complex, multifactorial condition that recognizes obesity as a chronic, relapsing disease influenced by biological, behavioral, cultural, and environmental factors. The ABCD framework emphasizes a patient-centered, holistic approach to diagnosis and treatment, moving beyond weight-centric models to address the systemic consequences of adiposity. Among therapeutic options, GLP-1 receptor agonists (GLP-1RAs) have emerged as a cornerstone in the management of ABCD by improving metabolic parameters and targeting the underlying pathophysiology of multiple interrelated conditions. GLP-1RAs enhance glycemic control and insulin sensitivity in type 2 diabetes while promoting weight loss and reducing cardiovascular risk by lowering blood pressure, improving lipid profiles, and reducing inflammation. They have shown efficacy in treating heart failure with preserved ejection fraction (HFpEF), particularly in patients with obesity. In metabolic dysfunction-associated steatotic liver disease (MASLD), GLP-1RAs reduce hepatic steatosis and inflammation, while in polycystic ovary syndrome (PCOS), they improve ovulation and menstrual regularity. Additionally, GLP-1RAs support kidney function preservation in chronic kidney disease (CKD) through blood pressure and glucose regulation and anti-inflammatory effects. Hence, the pleiotropic benefits of GLP-1Ras extend across the eight ABCD pillars obesity, type 2 diabetes, cardiovascular disease/heart failure, MASLD, polycystic ovary syndrome/infertility, CKD, hypertension, and dyslipidaemia positioning GLP-1RAs as a versatile, disease-modifying therapy. Also, the availability of oral semaglutide has further enhanced accessibility and convenience in the long-term management of ABCD, especially for patients preferring non-injectable therapies. In this clinical review, we will discuss the therapeutic role of GLP-1RAs, with a focus on oral semaglutide, across the eight pillars of ABCD, highlighting their multisystem benefits beyond weight loss.