6-LB: Estimated Fluid Volume Status following Initiation of Empagliflozin in Patients with Type 2 Diabetes and Cardiovascular Disease

Abstract

Background: Sodium glucose co-transporter 2 inhibitors promote osmotic/natriuretic diuresis and reduce excess fluid volume, and this benefits cardiovascular outcomes. We sought to assess the effect of empagliflozin on estimated fluid volumes in patients with type 2 diabetes (T2D) and cardiovascular disease (CVD).Methods: In this post hoc analysis of the EMBLEM trial, we tested serial changes in estimated plasma volume (ePV) and estimated extracellular volume (eEV) from baseline to weeks 4, 12, and 24 following initiation of empagliflozin 10 mg/day (n=52), relative to placebo (n=53).Results: In an analysis using mixed-effects models for repeated measures, relative to placebo empagliflozin reduced ePV by -2.23% (95% CI -5.72 to 1.25) at week 4, -8.07% (-12.76 to -3.37) at week 12, and -5.60% (-9.87 to -1.32) at week 24; eEV by -70.3 mL (95% CI -136.8 to -3.8) at week 4, -135.9 mL (-209.6 to -62.3) at week 12, and -144.4 mL (-226.3 to -62.4) at week 24 (Figure). The effect of empagliflozin on these parameters was mostly consistent across various patient characteristics. The change in the log-scale N-terminal pro-brain natriuretic peptide concentration was positively correlated with change in ePV (r=0.351, p=0.015).Conclusions: Empagliflozin reduced estimated fluid volumes in patients with T2D and CVD regardless of their backgrounds, and this effect was maintained for 24 weeks.View largeDownload slideView largeDownload slide DisclosureA. Tanaka: Research Support; Self; GlaxoSmithKline plc., Speaker’s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc. K. Node: Research Support; Self; Asahi Kasei Corporation, Astellas Pharma Inc., Bayer Yakuhin, Ltd., Daiichi Sankyo Company, Limited, Medtronic, Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Co., Teijin Pharma Limited, Speaker’s Bureau; Self; Astellas Pharma Inc., AstraZeneca K. K., Bayer Yakuhin, Ltd., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly Japan K. K., Mitsubishi Tanabe Pharma Corporation, Novartis Pharma K. K., Ono Pharmaceutical Co., Ltd. Emblem trial investigators: n/a.FundingBoehringer Ingelheim; Eli Lilly and Company