Beyond Glucose Control: A Comprehensive Review of Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors in Heart Failure, Chronic Kidney Disease, and Nonalcoholic Fatty Liver Disease

Sodium-glucose cotransporter 2 (SGLT2) inhibitors were first introduced to enhance glycemic control in type 2 diabetes mellitus (T2DM). However, a series of large-scale cardiovascular and renal outcomes trials have revealed their substantial benefits in reducing heart failure (HF) hospitalizations, slowing chronic kidney disease (CKD) progression, and improving cardiorenal outcomes, even among non-diabetic populations. Early studies further suggest potential benefits in non-alcoholic fatty liver disease (NAFLD). In this comprehensive review, we synthesize the mechanistic basis, landmark trials, real-world evidence, and emerging guidelines that position SGLT2 inhibitors as cornerstone therapies in the management of HF and CKD, with growing research in NAFLD. By highlighting key clinical outcomes, safety profiles, and cost-effectiveness considerations, we underscore how SGLT2 inhibitors transcend their original role in glucose regulation to provide multifaceted protection across the cardiorenal-metabolic spectrum.