February 10, 2023Open Access

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

JPJürgen H. ProchaskaBoehringer Ingelheim (Germany)CJClaus JüngerJohannes Gutenberg University Mainz ASAndreas SchulzUniversity of Stuttgart

Structured PICO

Does empagliflozin improve left ventricular diastolic function (E/e' ratio) in patients with type 2 diabetes mellitus?

Population

144 adults (age 18-84 years) with type 2 diabetes mellitus and prevalent left ventricular diastolic dysfunction (lateral E/E´ ratio ≥8), mean age 68.9, 14.1% female, single-center (Germany). Key inclusion: stable glucose-lowering background therapy and/or dietary treatment for at least 12 weeks, HbA1c 6.5-10.0% (or 6.5-9.0% if drug-naive). Key exclusion: eGFR <45 ml/min/1.73m2, uncontrolled hyperglycemia.

Intervention

Empagliflozin 10 mg/day for 12 weeks in addition to concomitant medication

Comparator

Identical placebo for 12 weeks in addition to concomitant medication

Outcome

Change of left ventricular E/E´ ratio after 12 weeks of interventionsurrogate

Empagliflozin significantly improves left ventricular diastolic function (E/e' ratio) in patients with type 2 diabetes mellitus, providing mechanistic insight into its cardiovascular benefits.

Abstract

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 9.618.24/11.14, 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.

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