From Metabolic Syndrome to Cardiovascular-Kidney-Metabolic Syndrome and Systemic Metabolic Disorder: A Call to Recognize the Progressive Multisystemic Dysfunction.

The landscape of metabolic health has evolved dramatically in recent years. Once viewed as a collection of distinct conditions, disorders like obesity, type 2 diabetes, cardiovascular disease, chronic kidney disease, and fatty liver disease are now understood to share common pathophysiological roots. This review explores the transition from the traditional concept of metabolic syndrome toward more comprehensive and clinically relevant frameworks, namely, the cardiovascular-kidney-metabolic (CKM) syndrome proposed by the American Heart Association, and the systemic metabolic disorder (SMD) framework introduced by the European Atherosclerosis Society. Both models recognize the progressive, multisystemic nature of metabolic dysfunction, highlight the need for stage-based risk stratification, and emphasize early intervention. The authors discuss the central role of dysfunctional adiposity and ectopic fat in driving organ-specific damage, and examine the growing body of evidence supporting the use of novel therapies such as sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RA), and gastric inhibitory polypeptide (GIP)/GLP-1RA in delivering multiorgan protection. By comparing the CKM and SMD models, the authors highlight their complementary nature and shared call for a shift in clinical thinking away from isolated management and toward integrated, multidisciplinary care. As the burden of metabolic dysfunction continues to rise, the need to recognize obesity as a chronic disease and to develop practical, collaborative strategies across cardiology, nephrology, endocrinology, and hepatology becomes even more urgent. The rise of cardiometabolic medicine offers a timely and necessary response to this growing challenge, creating opportunities for better prevention, earlier detection, and improved outcomes for the patients.