Metformin in Heart Failure Without Diabetes

Inclusion Criteria:

Patients with chronic heart failure (defined as >6 months duration) uptitrated to recommended or maximally tolerated dose of ACE-I/ARB (unless contraindicated) and beta-blocker (unless contraindicated). If indicated, an aldosterone receptor antagonist should be given (unless contraindicated). An ICD and/or CRT-D should be implanted, if indicated. Patients with a CRT device should be treated for > 3 months.
Reduced ejection fraction defined as LVEF < 40%
NYHA-class II or III with stable symptoms for at least the past 3 months
Renal Function by eGFR > 45 ml/min (MDRD equation) in accordance with FDA guidance on metformin use in CKD
Ability to understand the written patient information and to give informed consent
Negative urine-HCG for women of childbearing potential

Exclusion Criteria:

Patients with diabetes or insulin resistant, defined as 1 or more of the following criteria:

HbA1c >6.0% within the last 12 months prior to enrollment
Impaired fasting insulin resistance index (HOMA-IR) >2.7
Any oral or injectable hypoglycemic therapy (e.g. insulin, sulfonylureas)
Recent Hospitalizations in the past 3 months
Metformin treatment within the last 3 months
eGFR below 45 in the prior 6 months
Known allergy to metformin or major side effects to metformin treatment
Acute myocardial infarction, unstable angina or revascularization < 3 months at the time of randomization
Planned coronary revascularization, heart surgery, CRT implantation or other intervention during the study period that would potentially affect the function of the heart
Significant, uncorrected cardiac valve disease
Cardiac arrest or life threatening ventricular arrhythmias within the last 3 months (unless treated with an ICD)
Atrial fibrillation with poorly controlled ventricular rate at rest (> 100 beats/min)
Hypertrophic or restrictive cardiomyopathy, infiltrative or storage myocardial disease, active myocarditis, or pericardial disease.
Planned major surgery
Female patients who are pregnant, nursing, or of childbearing potential while not practicing effective chemical contraceptive methods (i.e. oral, implanted, injectable, or transdermal contraceptive hormones; intrauterine device)
Current abuse of alcohol or drugs
Life-expectancy of less than 1 year due to co-existing morbid illness
Stroke within the last 6 months
Liver disease with P-ALAT >3 times upper normal limit (it is possible to repeat this measurement once within a month)
Significant comorbidity or issue that makes the patient unsuitable for participation as judged by the investigator