Larsen AH, Jessen N, Nørrelund H, et al. - Thirty-six heart failure and reduced ejection fraction (HFrEF) individuals were randomized to metformin (n = 19) or placebo (n = 17) for 3 months in addition to standard heart failure therapy in order to examine whether metformin treatment might raise myocardial efficiency (stroke work/myocardial oxygen intake) in insulin-resistant individuals with HFrEF without diabetes. In non-diabetic HFrEF individuals, by decreasing myocardial oxygen intake, metformin treatment enhanced myocardial efficiency. Moreover, the measurement of circulating metformin levels distinguished responders from non-responders. Further, these energy-sparing impacts of metformin encourage additional large-scale examinations in heart failure individuals without diabetes.