Effects of empagliflozin on left ventricular diastolic function in addition to usual care in individuals with type 2 diabetes mellitus—results from the randomized, double-blind, placebo-controlled EmDia trial

• Published in: Clinical research in cardiology Vol. 112; no. 7; pp. 911 - 922
• Main Authors: Prochaska, Jürgen H., Jünger, Claus, Schulz, Andreas, Arnold, Natalie, Müller, Felix, Heidorn, Marc William, Baumkötter, Rieke, Zahn, Daniela, Koeck, Thomas, Tröbs, Sven-Oliver, Lackner, Karl J., Daiber, Andreas, Binder, Harald, Shah, Sanjiv J., Gori, Tommaso, Münzel, Thomas, Wild, Philipp S.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.07.2023; Springer Nature B.V
• Subjects: Aged; Antidiabetics; Blood pressure; Body weight; Cardiology; Congestive heart failure; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - diagnosis; Diabetes Mellitus, Type 2 - drug therapy; Diastolic pressure; Double-Blind Method; Double-blind studies; Ejection fraction; Erythrocytes; Female; Glucose transporter; Heart failure; Heart Failure - complications; Heart Failure - diagnosis; Heart Failure - drug therapy; Hematocrit; Hemoglobin; Humans; Male; Mathematical analysis; Medicine; Medicine & Public Health; Middle Aged; NCT; NCT02932436; Original Paper; Placebos; Pressure effects; Sodium-Glucose Transporter 2 Inhibitors - adverse effects; Stroke Volume; Subgroups; Treatment Outcome; Uric acid; Ventricle; Ventricular Function, Left; Heart failure; Diastolic function; Biomarkers; Clinical trial; Type 2 diabetes mellitus
• ISSN: 1861-0684; 1861-0692; 1861-0692
• DOI: 10.1007/s00392-023-02164-w

Background The sodium-glucose co-transporter 2 inhibitor empagliflozin improves cardiovascular outcome in patients with type 2 diabetes mellitus (T2DM) and heart failure. Experimental studies suggest a direct cardiac effect of empagliflozin associated with an improvement in left ventricular diastolic function. Methods In the randomized, double-blind, two-armed, placebo-controlled, parallel group trial EmDia, patients with T2DM and elevated left ventricular E / E ´ ratio were enrolled and randomized 1:1 to receive empagliflozin 10 mg/day versus placebo. The primary endpoint was the change of left ventricular E / E ´ ratio after 12 weeks of intervention. Results A total of 144 patients with T2DM and an elevated left ventricular E / e ´ ratio (age 68.9 ± 7.7 years; 14.1% women; E / e ´ ratio 9.61[8.24/11.14], left ventricular ejection fraction 58.9% ± 5.6%). After 12 weeks of intervention, empagliflozin resulted in a significant higher decrease in the primary endpoint E / e ´ ratio by − 1.18 ([95% confidence interval (CI) − 1.72/− 0.65]; P  < 0.0001) compared with placebo. The beneficial effect of empagliflozin was consistent across all subgroups and also occurred in subjects with heart failure and preserved ejection fraction ( n  = 30). Additional effects of empagliflozin on body weight, HbA1c, uric acid, red blood cell count, hemoglobin, mean corpuscular hemoglobin, and hematocrit were detected (all P  < 0.001). Approximately one-third of the reduction in E / e ´ by empagliflozin could be explained by the variables examined. Conclusions Empagliflozin improves diastolic function in patients with T2DM and elevated end-diastolic pressure. Since the positive effects were consistent in patients with and without heart failure with preserved ejection fraction, the data add a mechanistic insight for the beneficial cardiovascular effect of empagliflozin. Trial registration Clinicaltrials.gov, unique identifier: NCT02932436. Graphical abstract