SGLT2 inhibitor role in cardio-metabolic-renal diseases: a narrative review of recent evidence and their pharmacological, clinical and economic implications

Cardio-metabolic-renal (CMR) conditions, including type 2 diabetes mellitus, cardiovascular disease and chronic kidney disease, represent some of the most pressing public health challenges of the 21st century. In recent years, sodium-glucose co-transporter 2 (SGLT2) inhibitors (SGLT2is) have emerged as promising therapeutic agents across these interconnected disease areas. In Europe, the four currently approved SGLT2is for the treatment of type 2 diabetes mellitus - dapagliflozin, empagliflozin, canagliflozin and ertugliflozin - all have demonstrated cardiovascular and renal benefits in large cardiovascular outcomes trials. Notably, empagliflozin and dapagliflozin have also received approval for the treatment of heart failure and chronic kidney disease. This narrative review provides an overview of the role of SGLT2is in the management of CMR diseases. Overall, SGLT2is have demonstrated consistent cardiovascular safety and clinically meaningful benefits in selected outcomes across CMR conditions, with variations amongst individual agents reflecting differences in trial populations, study design and approved indications. This review summarizes current evidence to support individualized therapeutic decision-making rather than comparative positioning within the class.