title: The effect of metformin on insulin resistance and exercise parameters in patients with heart failure.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  NCT00473876.
authors: Centre for Cardiovascular and Lung Biology, Division of Medical Sciences, University of Dundee, Ninewells Hospital & Medical School, UK.
authors: Aaron K F
authors: AK
authors: Wong
authors: Ruth
authors: R
authors: Symon
authors: Matlooba A
authors: MA
authors: AlZadjali
authors: Donald S C
authors: DS
authors: Ang
authors: Simon
authors: S
authors: Ogston
authors: AnnaMaria
authors: A
authors: Choy
authors: John R
authors: JR
authors: Petrie
authors: Allan D
authors: AD
authors: Struthers
authors: Chim C
authors: CC
authors: Lang
mesh_terms: D000368:Aged; D003920:Diabetes Mellitus / Q000473:pathology; D004311:Double-Blind Method; D015444:Exercise; D005080:Exercise Test; D017079:Exercise Tolerance / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007333:Insulin Resistance; D008297:Male; D008687:Metformin / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D010101:Oxygen Consumption; D013223:Statistics as Topic; D013318:Stroke Volume; D016277:Ventricular Function, Left
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin