SGLT2 Inhibitors in Cardiovascular-Kidney-Metabolic Syndrome: Drugs Unifying Heart, Kidney, and Metabolism Pharmacotherapy.

Cardiovascular-kidney-metabolic syndrome describes a complex interplay between cardiovascular disease, chronic kidney disease, and metabolic disorders. Recent randomized controlled trials have demonstrated beneficial effects of SGLT2 inhibitors in patients with this multifaceted condition. This review aims to critically evaluate the available evidence supporting the role of SGLT2 inhibitors in patients with cardiovascular-kidney-metabolic syndrome and familiarize healthcare providers with the evidence surrounding significant renal and cardiac benefits of SGLT2 inhibitors. A comprehensive narrative literature review was conducted using PubMed. Eligible studies included randomized controlled trials, systematic reviews, and meta-analyses published in English between 2018 and 2025, focusing on SGLT2 inhibitors in the context of cardio-renal syndrome and cardio-kidney-metabolic syndrome. Multiple landmark trials have shown that SGLT2 inhibitors significantly reduce the risk of chronic kidney disease progression, MACE, and hospitalization for HF. These benefits were seen in patients both with and without type 2 diabetes. Importantly, SGLT2 inhibitors such as canagliflozin, dapagliflozin, empagliflozin, and sotagliflozin were well tolerated, though caution is advised in volume-depleted patients or those at risk for genitourinary infections. Positive effects, ranging from glycemic control to renoprotective and cardioprotective properties, support SGLT2 inhibitors as first-line therapy in improving clinical outcomes and quality of life in patients affected by this interconnected disease spectrum.