Cardio-Kidney-Metabolic Syndrome and Role of Oral Semaglutide

Cardiovascular–kidney–metabolic (CKM) syndrome, recently defined by the American Heart Association, reflects the interdependent progression of metabolic dysfunction, chronic kidney disease, and cardiovascular disease, with obesity, dysglycemia, hypertension, and dyslipidemia acting as key drivers. This chapter examines the relevance of CKM syndrome in the Indian context, where higher visceral adiposity, central obesity, and cardiometabolic risk at lower Body Mass Index thresholds make early identification and integrated management particularly important. The chapter positions oral semaglutide within this framework as a therapeutic option that addresses the metabolic initiator of CKM while also influencing downstream renal and cardiovascular risk. Evidence from the Peptide Innovation for Early Diabetes Treatment (PIONEER) program, including PIONEER 5 and PIONEER 6, together with real-world and emerging outcomes data such as Semaglutide cardiovascular Outcomes trial (SOUL), supports oral semaglutide for reductions in HbA1c, body weight, systolic blood pressure, inflammatory markers, albuminuria, and major adverse cardiovascular events, with additional signals for benefit in metabolic dysfunction-associated steatohepatitis (MASH)-related parameters. Collectively, these data support oral semaglutide as a practical and clinically relevant option for integrated risk reduction across the CKM continuum, particularly in patients with type 2 diabetes, obesity, and high cardiometabolic burden in routine practice.