Cardioprotective and Metabolic Effects of Metformin in Patients With Heart Failure and Diabetes

40 patients with HF and DM without previous diabetes treatment will be randomized into 2 groups (A succession: MET-placebo, B succession: placebo-MET) - stratified randomization with following parameters weighted: HF etiology (ischemic /non-ischemic), diabetes duration, gender, BMI, age, NYHA, smoker/non-smoker). After 3 months the treatment will be switched. All participants will undergo standardized selection of metabolic and cardiovascular tests (hyperinsulinemic euglycemic clamp with indirect calorimetry, measurement of endothelial function, echocardiography, spiroergometry, proton/phosphor MR spectroscopy, adipose tissue biopsy, selected cytokines in plasma and adipose tissue at the beginning and the end of each intervention period (3 times in total).

Inclusion criteria

• chronic heart failure will be defined by the following criteria (all must be included):

• diagnosis of HF known for at least 6 months
• medical history of hospitalization for cardiac decompensation with need for parenteral therapy for congestion - X-ray findings or swelling of lower extremities
• stable drug therapy at least 1 month
• treatment with diuretics (thiazide or furosemide)
• LVEF below 50%
• the presence of diabetes will be defined by:

• diagnosis and treatment of type 2 diabetes in the medical history
• screening blood sample:

• the value of HbA1c(according to IFCC)≥ 4.8% + fasting glucose ≥ 7.0 mmol / l in venous plasma or
• the value of HbA1c ≥ 4.8%(according to IFCC) + random blood glucose ≥ 11.1 mmol/l in venous plasma
• or OGTT - blood glucose level at 120 min ≥ 11.1 mmol/l OGTT is indicated just in case of positivity of one of the criteria (fasting glucose + HbA1c or HbA1c + random blood glucose)
• treatment of diabetes - by diet only
• women and men aged 40-70 years
• body mass index (kg/m2) in the range of 20-35
• the range of HbA1c between 4-6,5% IFCC
• signed informed consent

Exclusion criteria

• the planned cardiac intervention during the study that affect the function of the heart (revascularization including PCI, heart surgery, implantation of pacemaker, RF ablation; urgent candidate for OTS
• metabolic disease, including: 1 type diabetes, decompensated thyreopathy (Note: patients with hypothyroidism and stable substitution (the last 3 months) of normal TSH levels may participate in the study
• treatment with insulin or PAD one month before the recruitment(patients who were temporarily treated with insulin during hospitalization may participate in the study)
• pregnancy (positive β-HCG test), breast feeding, trying to become pregnant
• clinically significant anemia with hemoglobin below 100 g/l
• renal insufficiency with eGF below 0.7 ml/s
• atrial fibrillation - present during screening test
• the presence of other medical condition, which occurs during physical examination, laboratory tests, ECG, including pulmonary, neurological or inflammatory disease, which would be considered by the examiner to distort the consistency of data