title: Impact of metformin on peak aerobic capacity.
abstract: Individually, exercise and the drug metformin have been shown to prevent or delay type 2 diabetes. Metformin mildly inhibits complex I of the electron transport system and may impact aerobic capacity in people exercising while taking metformin. The purpose of the study was to evaluate the effects of metformin on maximal aerobic capacity in healthy individuals without mitochondrial dysfunction. Seventeen healthy, normal-weight men (n=11) and women (n=6) participated in a double-blind, placebo-controlled, cross-over design. Peak aerobic capacity was measured twice using a continuous, incrementally graded protocol; once after 7-9 d of metformin (final dose=2000 mg/d) and once with placebo, with 1 week between tests. The order of the conditions was counterbalanced. Peak oxygen uptake (VO2 peak), heart rate (HR), ventilation (VE), respiratory exchange ratio (RER), rating of perceived exertion (RPE), and test duration were compared across conditions using paired t tests with the R statistical program. VO2 peak (-2.7%), peak heart rate (-2.0%), peak ventilation (-6.2%), peak RER (-3.0%), and exercise duration (-4.1%) were all reduced slightly, but significantly, with metformin (all p<0.05). There was no effect of metformin on RPE or ventilatory breakpoint. Correlations between the decrement in VO2 peak and any of the other outcome variables were weak (r2<0.20) and not significant. Short-term treatment with metformin has statistically significant, but physiologically subtle, effects that reduce key outcomes related to maximal exercise capacity. Whether this small but consistent effect is manifested in people with insulin resistance or diabetes who already have some degree of mitochondrial dysfunction remains to be determined.
authors.affiliation: Energy Metabolism Laboratory, Department of Kinesiology, School of Public Health and Health Sciences, 107 Totman Building, University of Massachusetts, Amherst, MA 01003, USA. bbraun@kin.umass.edu
authors.forename: Barry
authors.initials: B
authors.lastname: Braun
authors.forename: Pamela
authors.initials: P
authors.lastname: Eze
authors.forename: Brooke R
authors.initials: BR
authors.lastname: Stephens
authors.forename: Todd A
authors.initials: TA
authors.lastname: Hagobian
authors.forename: Carrie G
authors.initials: CG
authors.lastname: Sharoff
authors.forename: Stuart R
authors.initials: SR
authors.lastname: Chipkin
authors.forename: Benjamin
authors.initials: B
authors.lastname: Goldstein
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000517:prevention & control; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors; D015444:Exercise / Q000502:physiology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D010101:Oxygen Consumption / Q000187:drug effects*; D010919:Placebos; D011659:Pulmonary Gas Exchange / Q000187:drug effects
chemical_list: D007004:Hypoglycemic Agents; D010919:Placebos; D008687:Metformin; D042967:Electron Transport Complex I