Effects of Metformin Treatment on Myocardial Efficiency in Patients With Heart Failure (METRONOME)

Aarhus University Hospital

Status and phase

Completed

Phase 2

Conditions

Heart Failure, Systolic

Treatments

Drug: Metformin

Drug: Placebo

Study type

Interventional

Funder types

Other

Identifiers

NCT02810132

2015-588

Details and patient eligibility

About

The study evaluates the effects of metformin treatment on myocardial efficiency in heart failure patients. 36 patients will be randomized to three months of metformin or placebo treatment in addition to their regular therapy.

Hypothesis: Treatment with metformin in patients with heart failure has direct or indirect beneficial effects on left ventricular myocardial oxidative metabolism, myocardial efficiency and contractile function.

Full description

Background: Heart failure (HF) is a common disease and diabetes/insulin resistance are present in approximately 50 % of HF patients. Metformin is the most commonly prescribed oral anti-diabetic drug, and registry and experimental studies show beneficial effects of metformin in HF, but randomized trials are needed.

Objectives: To investigate if treatment with metformin in patients with HF has beneficial effects on myocardial efficiency,

Design: A randomized, double-blind, placebo-controlled, single-center design. 36 patients with systolic heart failure will be randomized to either metformin (N = 18) or placebo (N= 18) for 3 months.

Methods: Patients will undergo echocardiography at rest and during exercise along with [11C]-acetate PET.

Primary outcome parameter is changes in myocardial external efficiency from visit 1 to 3 months of therapy.

Enrollment

36 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients with chronic heart failure 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 should be implanted, if indicated. Patients with a CRT device should be treated for > 3 months.
LVEF < 45%
NYHA-class II, III or IV
Relatively preserved renal function (eGFR > 30 ml/min)
Ability to understand the written patient information and to give informed consent
Negative urine-HCG for women of childbearing potential
Patients must have insulin resistance, defined as 1 or more of the following criteria:
1. HbA1c 5.5 - 6.4% (37 - 47 mmol/mol) within the last 12 months prior to enrolment
2. Impaired fasting glucose (IFG): Fasting P-glucose 5.6 - 6.9 mmol/l within 12 months prior to enrolment (patient in stable condition)
3. Impaired glucose tolerance (IGT) if OGTT has been performed at any time prior to enrolment: Fasting P-glucose < 7.0 mmol/l and 2 hour P-glucose 7.8 -11.0 mmol/l

Exclusion criteria

Metformin treatment within the last 3 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
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)
Age < 18 years
Current abuse of alcohol or drugs
Cancer, with a life-expectancy of less than 2 years
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
Participation in another study involving long-term medical intervention (participation in device studies is allowed)