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Diabetes drives an increasing burden of cardiovascular and renal disease worldwide, motivating the search for new hypoglycemic agents that confer cardiac and renal protective effects. Although initially developed as hypoglycemic agents, sodium-glucose co-transporter 2 (SGLT-2) inhibitors have since been studied in patients with and without diabetes for the management of heart failure and chronic kidney disease. A growing body of evidence supports the efficacy and safety of SGLT-2 inhibitors in patients with chronic kidney disease (CKD), based on complex mechanisms of action that extend far beyond glucosuria and that confer beneficial effects on cardiovascular and renal hemodynamics, fibrosis, inflammation, and end-organ protection. This review focuses on the pharmacology and pathophysiology of SGLT-2 inhibitors in patients with CKD, as well as their cardiovascular and renal effects in this population. We are focusing on the five agents that have been tested in cardiovascular outcome trials and that have been approved either in Europe or in North America: empagliflozin, dapagliflozin, canagliflozin, ertugliglozin, and sotagliflozin. [ABSTRACT FROM AUTHOR]