Background

Beneficial effects of empagliflozin, a sodium-glucose cotransporter 2 inhibitor, on cardiovascular and renal outcome in individuals with type 2 diabetes mellitus (T2DM) with and without heart failure are well-established. However, evidence on its impact on patient-reported outcome is lacking. The objective of this study was to assess the effects of empagliflozin compared with placebo on quality of life and mental well-being in T2DM patients with left ventricular diastolic dysfunction.

Methods

In the randomized, double-blind, two-arm, placebo-controlled, parallel group EmDia trial (CinicalTrials.gov: NCT02932436), T2DM patients with elevated left ventricular E/e’ ratio were randomized in a 1:1 manner to receive either empagliflozin (10mg/day) or placebo for 12 weeks. Participants underwent a highly standardized medical examination at baseline, after one week, and after 12 weeks. Data on quality of life (EQ-5D-5L), depressive symptoms (PHQ-9), somatic symptoms (PHQ-15), sleep quality (Jenkins Sleep Scale), and positive affect were collected by sequential questionnaire-based assessments. Adjusted linear regressions were performed to model the effects of empagliflozin on quality of life and mental well-being after 12 weeks.

Results

A total of N=144 participants were randomized (age 68.9±7.7 years; 14.1% women; median E/e' ratio 9.61 [interquartile range 8.24/11.14]; left ventricular ejection fraction 58.9%±5.6%; EQ-5D-5L score 0.94 [0.87/1.00]; EQ-5D visual analogue scale (VAS) 80.0 [65.8/85.0]). Significant between-group differences in changes from baseline to 12 weeks of intervention were identified in the EQ-5D-5L score (ß-estimate=0.043, 95% confidence interval [CI] 0.015-0.071) and EQ-5D VAS (ß-estimate=5.61, 95% CI 1.58-9.64) favoring empagliflozin. The effects of empagliflozin on quality of life were not mediated by improvement in body mass index, E/e’ ratio, and HbA1c. The beneficial impact of empagliflozin on the EQ-5D-5L score was more pronounced in individuals with insulin-dependent T2DM (ß-estimate=0.083, 95% CI 0.028-0.14). No effects of empagliflozin compared with placebo were observed in depressive and somatic symptomatology, sleep quality, and positive affect.

Conclusion

The present study demonstrated positive short-term effects of empagliflozin on quality of life in T2DM patients with left ventricular diastolic dysfunction. The findings support benefits of empagliflozin on patient-related outcome beyond its antidiabetic, cardio-, and renoprotective effects.