Background: Treatment with the sodium-glucose cotransporter-2 (SGLT2) inhibitors reduces heart failure hospitalization (HHF) in patients with type 2 diabetes (T2D). Early separation of HHF event curves suggests immediate effects of SGLT2 inhibition on cardiac function.

Aim: This study examined early and delayed effects of empagliflozin treatment on echocardiographic measures of cardiac function, including left ventricular systolic and diastolic function.

Methods: In this prospective, placebo-controlled, randomized, double blind, exploratory study patients with T2D were randomized into 2 groups and received empagliflozin 10 mg or placebo for a period of 3 months in addition to their concomitant medication. Echocardiographic parameters were assessed at baseline and after 1 day, 3 days and 3 months of treatment. Left ventricular systolic function (LV-EF) was measured by Simpson’s Biplane Method. Additionally we performed myocardial deformation analysis of the left ventricle to assess peak global longitudinal strain (GLS) of the endocardial layer. For diastolic function we determined early (E) and late (A) diastolic mitral inflow velocities, deceleration time (DT), septal early diastolic mitral annular tissue velocity (septal e’) and lateral early diastolic mitral annular tissue velocity (lateral e’) as well as calculated E/e' ratio and E/A ratio.
              
Results: Baseline characteristics were comparable in the empagliflozin (n=20) and placebo (n=22) group. Empagliflozin led to a significant increase in urinary glucose excretion (baseline: 7.3 ± 22.7 g/24 hrs; day 1: 48.4 ± 34.7 g/24 hrs; p<0.001) as well as urinary volume (1740 ± 601 mL/24 hrs to 2112 ± 837 mL/24 hrs; p=0.011) already after one day compared to placebo. Echocardiography showed no difference in left ventricular systolic function as assessed by left ventricular ejection fraction and strain analysis. However, empagliflozin significantly improved left ventricular diastolic function as assessed by a reduction of early mitral inflow velocity relative to early diastolic left ventricular relaxation (E/e’) which became already significant at day 1 of treatment (baseline: 9.2 ± 2.6; day 1: 8.5 ± 2.2; p=0.005) and remained apparent throughout the study. This was primarily attributable to reduced early mitral inflow velocity E (baseline: 0.8 ± 0.2 m/sec; day 1: 0.73 ± 0.2 m/sec; p=0.003).
       
Conclusion: Empagliflozin treatment of patients with T2D leads to a rapid and sustained improvement of diastolic function.