Effects of Empagliflozin on Exercise Capacity and Left Ventricular Diastolic Function in Patients With Heart Failure With Preserved Ejection Fraction and Type-2 Diabetes Mellitus

A Phase 4, Single-center, Randomized, Parallel Group Study to Assess Effects of Empagliflozin on Exercise Capacity and Left Ventricular Diastolic Function in Patients With Heart Failure With Preserved Ejection Fraction and Type-2 Diabetes Mellitus

Patients enrolled into the study will be randomly allocated either to Empagliflozin group or control group. In the Empagliflozin group patients will be receiving standard care + Empagliflozin 10 mg o.d., in the control group patients will be receiving standard care without sodium glucose contransporter 2 (SGLT2) inhibitors.

Inclusion Criteria:

1. Males and females aged 45 to 80 years at screening

2. Diagnosis of type-2 diabetes mellitus with stable glucose-lowering background therapy for at least 12 weeks

3. HbA1c ≥ 6,5% and ≤ 10% at screening

4. Diagnosis of HFpEF which includes:

   • Symptoms ± signs (as defined in 2016 European Society of Cardiology guidelines for the diagnosis and treatment of acute and chronic heart failure)
   • Ejection fraction ≥ 50% (by Simpson)
   • Increased LV filling pressures at rest or during exercise determined by echocardiography (LV diastolic dysfunction grade II/III and/or positive diastolic stress test) [according to American Society of Echocardiography and European Association of Cardiovascular Imaging (ASE/EACVI) Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography, 2016]

5. Signed and dated informed consent

Exclusion Criteria:

1. Pretreatment with empagliflozin or other SGLT-2 inhibitor within the last 2 months
2. Type-1 diabetes mellitus
3. NYHA classification IV or acute decompensated heart failure at screening
4. Impaired renal function, defined as eGFR <30 ml/min/1.73 m² of body-surface-area (CKD-EPI)
5. Systolic blood pressure > 180 mmHg or < 90 mmHg
6. Permanent atrial flutter or atrial fibrillation
7. Other conditions that may be responsible for impaired diastolic function such as hypertrophic/restrictive cardiomyopathy, constrictive pericarditis and etc.
8. Anemia (Hb < 100 g/l)
9. Myocardial infarction, coronary artery bypass graft surgery within the last 3 months
10. Stroke or TIA within the last 3 months
11. Indications of liver disease
12. Acute genital infection or urinary tract infection
13. Pregnancy
14. Additional exclusion criteria may apply