Dapagliflozin for the treatment of chronic kidney disease

Sodium-dependent glucose cotransporter 2 (SGLT2) is a glucose transporter expressed on the proximal tubular cells, where it reabsorbs glucose from the glomerular filtrate. SGLT2 inhibitors (SGLT2is), initially developed as an antidiabetic drug, have recently attracted considerable attention because they have cardiorenal protective effects. Among SGLT2is, dapagliflozin was the first to demonstrate the renoprotective effect in patients with and without diabetes and has been approved for chronic kidney disease (CKD) treatment.

This review covers the pharmacological characteristics and the clinical efficacy and safety profiles of dapagliflozin, including comparison with other SGLT2is and risk modification strategies.

In DAPA-CKD, dapagliflozin reduced the primary outcome (≥50% estimated glomerular filtration rate [eGFR] decline, end-stage kidney disease [ESKD], or renal or cardiovascular [CV] death) by 39% in CKD patients. This beneficial effect was consistent across prespecified subgroups, including those based on the presence of diabetes. Dapagliflozin also decreased the CV composite outcome and all-cause death by 29% and 31%, respectively. Although an increased risk of adverse events such as ketoacidosis and volume depletion has been reported, the robust renal and CV benefits of dapagliflozin are expected to outweigh potential risks. SGLT2is, including dapagliflozin, will constitute the mainstay of CKD treatment.