Commentary

Metformin improves glycaemic control in type 2 diabetes without causing weight gain or hypoglycaemia and is the only oral hypoglycaemic drug that has reduced cardiovascular morbidity and mortality in a randomised trial.¹ However, metformin might increase the risk for lactic acidosis. For this reason, many prescribing guidelines suggest that metformin should be contraindicated in patients at higher than average risk for lactic acidosis.

Salpeter et al hoped to compare the incidence of lactic acidosis in metformin users with those taking other medications or placebo, but this proved impossible because not a single case of lactic acidosis was found in any of these studies. Although many of the included studies did not specifically exclude people with renal, hepatic, cardiac, or pulmonary disease, it is possible that not enough people with these comorbid conditions were enrolled in the studies to allow accurate risk estimates. In Saskatchewan, where comprehensive, linkable databases of prescriptions and healthcare encounters are maintained, only 2 cases of lactic acidosis were found among 11 797 people who filled metformin prescriptions over a 15 year period (9 cases/100 000 patient-y).² This risk is strikingly similar to the lactic acidosis rate of 9.7/100 000 patient-years in a large US Health Maintenance Organisation in 1993 to 1994, when metformin was not yet available in the United States.³ Because >25% of people receiving metformin have ≥1 “absolute” contraindication to it,⁴ the low observed risk for lactic acidosis in metformin users cannot be attributed solely to “prudent” prescribing. In contrast to phenformin, no credible evidence exists that metformin increases the risk for lactic acidosis beyond what would be expected from underlying diseases. It is possible that overly restrictive contraindications to metformin might result in many people being denied an excellent drug while preventing few if any cases of lactic acidosis.