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A randomised, double‐blind, placebo‐controlled trial of metformin on myocardial efficiency in insulin‐resistant chronic heart failure patients without diabetes
Author(s) -
Larsen Anders Hostrup,
Jessen Niels,
Nørrelund Helene,
Tolbod Lars Poulsen,
Harms Hendrik Johannes,
Feddersen Søren,
Nielsen Flemming,
Brøsen Kim,
Hansson Nils Henrik,
Frøkiær Jørgen,
Poulsen Steen Hvitfeldt,
Sörensen Jens,
Wiggers Henrik
Publication year - 2020
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1002/ejhf.1656
Subject(s) - medicine , metformin , ejection fraction , heart failure , placebo , cardiology , diabetes mellitus , clinical endpoint , stroke volume , insulin , type 2 diabetes , endocrinology , randomized controlled trial , alternative medicine , pathology
Aims The present study tested the hypothesis that metformin treatment may increase myocardial efficiency (stroke work/myocardial oxygen consumption) in insulin‐resistant patients with heart failure and reduced ejection fraction (HFrEF) without diabetes. Methods and results Thirty‐six HFrEF patients (ejection fraction 37 ± 8%; median age 66 years) were randomised to metformin ( n = 19) or placebo ( n = 17) for 3 months in addition to standard heart failure therapy. The primary endpoint was change in myocardial efficiency expressed as the work metabolic index (WMI), assessed by 11 C‐acetate positron emission tomography and transthoracic echocardiography. Compared with placebo, metformin treatment (1450 ± 550 mg/day) increased WMI [absolute mean difference, 1.0 mmHg·mL·m ‐2 ·10 6 ; 95% confidence interval (CI) 0.1 to 1.8; P = 0.03], equivalent to a 20% relative efficiency increase. Patients with above‐median plasma metformin levels displayed greater WMI increase (25% vs. –4%; P = 0.02). Metformin reduced myocardial oxygen consumption (–1.6 mL O 2 ·100 g ‐1 ·min ‐1 ; P = 0.014). Cardiac stroke work was preserved (–2 J; 95% CI –11 to 7; P = 0.69). Metformin reduced body weight (–2.2 kg; 95% CI –3.6 to –0.8; P = 0.003) and glycated haemoglobin levels (–0.2%; 95% CI –0.3 to 0.0; P = 0.02). Changes in resting and exercise ejection fraction, global longitudinal strain, and exercise capacity did not differ between groups. Conclusion Metformin treatment in non‐diabetic HFrEF patients improved myocardial efficiency by reducing myocardial oxygen consumption. Measurement of circulating metformin levels differentiated responders from non‐responders. These energy‐sparing effects of metformin encourage further large‐scale investigations in heart failure patients without diabetes.