Differential pharmacology and clinical utility of dapagliflozin in type 2 diabetes

Ioanna Papakitsou,1 George Vougiouklakis,1 Moses S Elisaf,2 Theodosios D Filippatos1 1Department of Internal Medicine, School of Medicine, University of Crete, University Hospital of Heraklion, Heraklion, Crete, Greece; 2Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, GreeceCorrespondence: Theodosios D FilippatosDepartment of Internal Medicine, School of Medicine, University of Crete, University Hospital of Heraklion, Voutes, Crete, Heraklion, Crete 71500, GreeceTel +30 281 340 2817Email filtheo@uoc.grAbstract: Dapagliflozin belongs in the family of sodium-glucose cotransporter 2 (SGLT2) inhibitors and acts by reducing glucose reabsorption in the proximal tubule. The aim of this review is to present the differential pharmacology and clinical utility of dapagliflozin. Dapagliflozin is orally administered, has a long half-life of 12.9 hours and (similar to empagliflozin) is a much weaker SGLT1 inhibitor compared with canagliflozin. Dapagliflozin significantly decreases glycated hemoglobin and fasting glucose levels in patients with type 2 diabetes mellitus (T2DM). The drug improves body weight, blood pressure, uric acid, triglycerides and high-density lipoprotein cholesterol. In the DECLARE-TIMI 58 trial, a large trial of 17,160 T2DM patients with established cardiovascular disease (CVD) or without established CVD but with multiple risk factors, dapagliflozin compared with placebo resulted in a significantly lower rate of the composite outcome of CVD death or hospitalization for heart failure (HHF); this effect was mainly due to a lower rate of HHF in the dapagliflozin group (HR: 0.73; 95%CI: 0.61–0.88), whereas no difference was observed in the rate of CVD death (HR: 0.98; 95%CI: 0.82–1.17). Moreover, dapagliflozin was noninferior to placebo with respect to major adverse CVD events. Dapagliflozin exerts beneficial effects on albuminuria. Additionally, in the DECLARE-TIMI 58 trial it significantly reduced the composite renal endpoint (40% decrease in glomerular filtration rate, end stage renal disease, or renal death) in both patients with established CVD and patients with multiple risk factors (overall HR: 0.53; 95%CI: 0.43–0.66). However dapagliflozin, like the other SGLT2 inhibitors, is associated with an increased risk of genital and urinary tract infections (usually mild mycotic infections) and acute kidney injury in cases of reduced extracellular volume. Dapagliflozin is a useful antidiabetic treatment which also exerts beneficial effects in the management of heart failure and diabetic kidney disease.Keywords: dapagliflozin, sodium-glucose cotransporter 2, cardiovascular disease, diabetes, kidney, adverse effects