Diabetologie und Stoffwechsel 2016; 11 - P33
DOI: 10.1055/s-0036-1580780

Contrasting influences of renal function on blood pressure and HbA1c reductions with empagliflozin: Pooled analysis of phase III trials

D Cherney 1, ME Cooper 2, S Crowe 3, OE Johansen 4, SS Lund 3, HJ Woerle 3, UC Broedl 3, T Hach 3
  • 1Toronto General Hospital, University of Toronto, Toronto, Canada
  • 2Baker IDI Heart and Diabetes Institute, Melbourne, Australia
  • 3Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany
  • 4Boehringer Ingelheim Norway KS, Asker, Norway

Objective: Glucose lowering with empagliflozin is dependent on renal function. We investigated the influence of chronic kidney disease (CKD) on changes in HbA1c and blood pressure (BP) with empagliflozin.

Methods: Using pooled data from five, 24-week randomized Phase III trials in patients with type 2 diabetes (T2DM), we assessed changes from baseline in systolic BP (SBP) and HbA1c with empagliflozin 25 mg versus placebo in subgroups by baseline eGFR (MDRD equation; normal renal function [≥90 mL/min/1.73 m2], stage 2 CKD [≥60 to < 90 mL/min/1.73 m2], stage 3 CKD [≥30 to < 60 mL/min/1.73 m2] and stage 4 CKD [< 30 mL/min/1.73 m2]).

Results: In patients with normal renal function, or stage 2 or 3 CKD, empagliflozin significantly reduced HbA1c and SBP versus placebo. As expected, placebo-corrected HbA1c reductions with empagliflozin decreased with decreasing eGFR (normal renal function: -0.84% [95% CI -0.95,-0.72]; stage 2 CKD: -0.60% [95% CI -0.70,-0.51]; stage 3 CKD: -0.38% [95% CI -0.52,-0.24]; stage 4 CKD: -0.04% [95% CI -0.37, 0.29]). In contrast, placebo-corrected SBP reductions with empagliflozin appeared to be maintained with decreasing eGFR (normal renal function: -3.2 mmHg [95% CI -4.9,-1.5]; stage 2 CKD: -4.0 mmHg [95% CI -5.4,-2.6]; stage 3 CKD: -5.5 mmHg [95% CI -7.6,-3.4]; stage 4 CKD: -6.6 mmHg [95% CI -11.4,-1.8]).

Conclusion: Unlike HbA1c, SBP reductions with empagliflozin in patients with T2DM appeared to be maintained in patients with lower eGFR. SBP modulation with empagliflozin may involve pathways other than urinary glucose excretion such as natriuresis, weight loss, reduced arterial stiffness or direct vascular effects.