Effect of empagliflozin on left ventricular contractility and peak oxygen uptake in subjects with type 2 diabetes without heart disease: results of the EMPA-HEART trial
Lorenzo Nesti, Nicola Riccardo Pugliese, Paolo Sciuto, Domenico Tricò, Angela Dardano, Simona Baldi, Silvia Pinnola, Iacopo Fabiani, Vitantonio Di Bello, Andrea Natali
Abstract
Abstract Background The mechanism through which sodium-glucose cotransporter 2 inhibitors (SGLT2i) prevent the incidence of heart failure and/or affect cardiac structure and function remains unclear. Methods The EMPA-HEART trial is aimed at verifying whether empagliflozin improves myocardial contractility (left ventricle global longitudinal strain, LV-GLS) and/or cardiopulmonary fitness (peak oxygen uptake, VO2peak) in subjects with type 2 diabetes (T2D) without heart disease. Patients with T2D, normal LV systolic function (2D-Echo EF > 50%), and no heart disease were randomized to either empagliflozin 10 mg or sitagliptin 100 mg for 6 months and underwent repeated cardiopulmonary exercise tests with echocardiography and determination of plasma biomarkers. Results Forty-four patients completed the study, 22 per arm. Despite comparable glycaemic control, modest reductions in body weight (− 1.6; [− 2.7/− 0.5] kg, p = 0.03) and plasma uric acid (− 1.5; [− 2.3/− 0.6], p = 0.002), as well as an increase in haemoglobin (+ 0.7; [+ 0.2/+ 1.1] g/dL, p = 0.0003) were evident with empagliflozin. No difference was detectable in either LV-GLS at 1 month (empagliflozin vs sitagliptin: + 0.44; [− 0.10/+ 0.98]%, p = 0.11) and 6 months of therapy (+ 0.53; [− 0.56/+ 1.62]%), or in VO 2peak (+ 0.43; [− 1.4/+ 2.3] mL/min/kg, p = 0.65). With empagliflozin, the subgroup with baseline LV-GLS below the median experienced a greater increase (time*drug p < 0.05) in LV-GLS at 1 month (+ 1.22; [+ 0.31/+ 2.13]%) and 6 months (+ 2.05; [+ 1.14/+ 2.96]%), while sitagliptin induced a modest improvement in LV-GLS only at 6 months (+ 0.92; [+ 0.21/+ 0.62]%). Conclusions Empagliflozin has neutral impact on both LV-GLS and exercise tolerance in subjects with T2D and normal left ventricular function. However, in patients with subclinical dysfunction (LV-GLS < 16.5%) it produces a rapid and sustained amelioration of LV contractility. Trial registration EUDRACT Code 2016-002225-10