Randomized, placebo-controlled trial on the renal and systemic hemodynamic effects of empagliflozin

Abstract

IntroductionSodium-glucose cotransporter 2 inhibitors (SGLT2i) improve renal outcomes in type 2 diabetes (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. MethodsUsing a double-blind placebo controlled cross-over design we randomized patients with DM2 and estimated glomerular filtration rate (eGFR) >60 ml/min/1.73m2 (n=16), patients with DM2 and eGFR 20-60 ml/min/1.73m2 (n=17) and patients with non-diabetic CKD and eGFR 20-60 ml/min/1.73m2 (n=16) to empagliflozin 10 mg daily or placebo for four weeks and crossed over to the opposite treatment after two-week washout. RBF was measured with 82Rubidium-positron emission-tomography/computed-tomography, GFR with 99mTechnetium-diethylene-triamine-pentaacetate-clearance. 24-hour blood pressure (BP) and total vascular resistance (TVR) were recorded using a Mobil-O-graph. ResultsCompared to placebo empagliflozin reduced RBF by 6% in the DM2-CKD group (p<0.001) with non-significant decreases of 4% in the DM2 group and 1% in the CKD group (p=0.29 and 0.72). Empagliflozin reduced GFR, BP and TVR in all groups, while renal vascular resistance (RVR) remained unchanged ConclusionEmpagliflozin 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 pre-glomerular and post-glomerular effects.