Randomized, Placebo-Controlled Trial on the Renal and Systemic Hemodynamic Effects of Empagliflozin

Introduction: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve renal outcomes in type 2 diabetes mellitus (DM2) and chronic kidney disease (CKD). A decrease in renal blood flow (RBF) with attenuation of glomerular hyperfiltration may contribute. We examined renal and systemic hemodynamic effects of SGLT2i in relevant patient categories. Methods: Using a double-blind placebo controlled cross-over design, we randomized patients with DM2 and estimated glomerular filtration rate (eGFR) > 60 ml/min per 1.73 m(2) (n = 16), patients with DM2 and eGFR from 20 to 60 ml/min per 1.73 m(2) (n = 17), and patients with nondiabetic CKD and eGFR from 20 to 60 ml/min per 1.73 m(2) (n = 16) to empagliflozin 10 mg daily or placebo for 4 weeks and crossed over to the opposite treatment after 2-week washout. RBF was measured with (82)Rubidium-positron emission-tomography/computed-tomography, glomerular filtration rate (GFR) with (99m)Technetium-diethylene-triamine-pentaacetate-clearance. A Mobil-O-graph was used to record 24-hour blood pressure (BP) and total vascular resistance (TVR). Results: Compared to placebo, empagliflozin reduced RBF by 6% in the DM2-CKD group (P < 0.001) with nonsignificant decreases of 4% in the DM2 group and 1% in the CKD group (P = 0.29 and 0.72, respectively). Empagliflozin reduced GFR, BP, and TVR in all groups, whereas renal vascular resistance (RVR) remained unchanged. Conclusion: Empagliflozin reduced RBF in patients with DM2 and CKD, whereas GFR, BP, and TVR were reduced in all groups. This pattern, together with a lack of reduction in RVR, suggests SGLT2i protect the glomerulus through combined preglomerular and post glomerular effects.