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The effect of metformin on insulin resistance and exercise parameters in patients with heart failure
Author(s) -
Wong Aaron K.F.,
Symon Ruth,
AlZadjali Matlooba A.,
Ang Donald S.C.,
Ogston Simon,
Choy AnnaMaria,
Petrie John R.,
Struthers Allan D.,
Lang Chim C.
Publication year - 2012
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 - 10.1093/eurjhf/hfs106
Subject(s) - medicine , metformin , heart failure , ejection fraction , placebo , insulin resistance , clinical endpoint , cardiology , insulin , endocrinology , randomized controlled trial , alternative medicine , pathology
Aims Chronic heart failure (CHF) is an insulin‐resistant state. The degree of insulin resistance (IR) correlates with disease severity and is associated with reduced exercise capacity. In this proof of concept study, we have examined the effect of metformin on IR and exercise capacity in non‐diabetic CHF patients identified to have IR. Methods and results In a double‐blind, placebo‐controlled study, 62 non‐diabetic IR CHF patients (mean age, 65.2 ± 8.0 years; male, 90%; left ventricular ejection fraction, 32.6 ± 8.3%; New York Heart Association class I/II/III/IV, 11/45/6/0) were randomized to receive either 4 months of metformin ( n = 39, 2 g/day) or matching placebo ( n = 23). IR was defined by a fasting insulin resistance index (FIRI) ≥2.7. Cardiopulmonary exercise testing and FIRI were assessed at baseline and after 4 months of intervention. Compared with placebo, metformin decreased FIRI (from 5.8 ± 3.8 to 4.0 ± 2.5, P < 0.001) and resulted in a weight loss of 1.9 kg ( P < 0.001). The primary endpoint of the study, peak oxygen uptake (VO 2 ), did not differ between treatment groups. However, metformin improved the secondary endpoint of the slope of the ratio of minute ventilation to carbon dioxide production (VE/VCO 2 slope), from 32.9 ± 15.9 to 28.1 ± 8.8 ( P = 0.034). In the metformin‐treated group, FIRI was significantly related to the reduction of the VE/VCO 2 slope ( R = 0.41, P = 0.036). Conclusion Metformin treatment significantly improved IR but had no effect on peak VO 2 , the primary endpoint of our study. However, metformin treatment did result in a significant improvement in VE/VCO 2 slope. Trial registration: NCT00473876.