Effects of empagliflozin on cardiorespiratory fitness and significant interaction of loop diuretics

The effects of empagliflozin on cardiorespiratory fitness in patients with type 2 diabetes mellitus (T2DM) and heart failure with reduced ejection fraction (HFrEF) are unknown. In this pilot study we determined the effects of empagliflozin 10mg/d for 4weeks on peak oxygen consumption (VO2) in 15 patients with T2DM and HFrEF. As an exploratory analysis, we assessed whether there was an interaction of the effects of empagliflozin on peak VO2 of loop diuretics. Empagliflozin reduced body weight (-1.7kg; P=.031), but did not change peak VO2 (from 14.5mL kg(-1) min(-1) [12.6-17.8] to 15.8 [12.5-17.4] mLkg(-1) min(-1); P=.95). However, patients using loop diuretics (N=9) demonstrated an improvement, whereas those without loop diuretics (N=6) experienced a decrease in peak VO2 (+0.9 [0.1-1.4] vs -0.9 [-2.1 to -0.3] mLkg(-1) min(-1); P=.001), and peak VO2 changes correlated with the baseline daily dose of diuretics (R=+0.83; P<.001). Empagliflozin did not improve peak VO2 in patients with T2DM and HFrEF. However, as a result of exploratory analysis, patients concomitantly treated with loop diuretics experienced a significant improvement in peak VO2.