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The aim of the study is to evaluate the effect of metformin on myocardial function, insulin resistance and selected metabolic markers in patients with type 2 diabetes and heart failure (HF+DM+) in a cross-over, randomized, placebo controlled trial.
Hypothesis:
Metformin treatment in HF+DM+ group will lead to better myocardial function and load tolerance in comparison to placebo. The degree of improvement will be linked to selected metabolic parameters.
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Metformin | Experimental | 500 mg per day(1/2 tbl 1000 mg once a day - in the morning) after a week increase the dose to 1 tbl á 1000 mg after two weeks increase the dose to 2 x tbl 1000 mg (in the morning and in the evening), duration: 3 months |
|
| Placebo | Placebo Comparator | 500 mg per day(1/2 tbl 1000 mg once a day - in the morning) after a week increase the dose to 1 tbl á 1000 mg after two weeks increase the dose to 2 x tbl 1000 mg (in the morning and in the evening), duration:3 months |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Metformini hydrochloridum (Siofor 1000 tbl, Berlin) | Drug | Patients will be randomized into 2 groups (A succession: MET-placebo, B succession: placebo-MET. After 3 months the treatment will be switched. Titration: 500 mg per day(1/2 tbl 1000 mg once a day - in the morning) after a week increase the dose to 1 tbl á 1000 mg after two weeks increase the dose to 2 x tbl 1000 mg (in the morning and in the evening) |
| Measure | Description | Time Frame |
|---|---|---|
| insulin sensitivity | change of glucose disposal during clamp | at baseline and after 3 months |
| Measure | Description | Time Frame |
|---|---|---|
| energy expenditure | change of energy expenditure measured by indirect calorimetry | at baseline and after 3 months |
| endothelial function | change in digital pulse amplitude tonometry |
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Inclusion Criteria:
chronic heart failure will be defined by the following criteria (all must be included):
the presence of diabetes will be defined by:
diagnosis and treatment of type 2 diabetes in the medical history
screening blood sample:
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:
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| Name | Affiliation | Role |
|---|---|---|
| Terezie Pelikanova, Prof., MD | Diabetes Center, Institute of Clinical and Experimental Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Diabetes Center, Institute of Clinical and Experimental Medicine | Prague | Czechia |
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| ID | Term |
|---|---|
| D007333 | Insulin Resistance |
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| placebo | Drug | Patients will be randomized into 2 groups (A succession: MET-placebo, B succession: placebo-MET. After 3 months the treatment will be switched. |
|
| at baseline and after 3 months |
| heart function | change measured by echocardiography and spiroergometry | at baseline and after 3 months |
| D003920 | Diabetes Mellitus |
| D004700 | Endocrine System Diseases |