The safety of metformin in heart failure.

OBJECTIVE To examine the evidence regarding the safety of metformin in heart failure. DATA SOURCES Searches in MEDLINE and International Pharmaceutical Abstracts were performed (1966-February 2007). Search terms included metformin, heart failure, lactic acidosis, clinical trials, and insulin resistance. STUDY SELECTION AND DATA EXTRACTION Published studies and case reports that evaluated the causal link between metformin and lactic acidosis in patients with heart failure were selected for review. DATA SYNTHESIS There were no case reports of patients who had metformin-associated lactic acidosis when heart failure was the only contraindication. Two large retrospective studies showed that metformin does not increase the risk of lactic acidosis in patients with heart failure. However, these retrospective analyses did not account for many important confounding variables. A reduction in mortality rates in metformin users with New York Heart Association Class III and IV heart failure was observed in one small (N = 94) prospective trial. CONCLUSIONS Results from 3 trials suggest that metformin may be safe to use in heart failure. Large prospective trials are needed to provide conclusive evidence regarding metformin's safety. Until then, use of metformin in heart failure patients should not be recommended routinely. If it is used in patients with heart failure, they should be monitored closely for signs of lactic acidosis.