Limitations of metformin use in patients with kidney disease: are they warranted?

To show that metformin, one of the most widely used agents, is contraindicated in patients with diabetes having chronic kidney disease (CKD) (i.e. serum creatinine >1.5 mg/dl) secondary to fear of lactic acidosis. The overall incidence of lactic acidosis is estimated at an upper limit of eight cases per 100 000 patient-years. We evaluated metformin use in two cohorts, one from the University of Chicago Diabetes Center and the other from National Health and Nutrition Examination Survey (NHANES) 1999-2006.

Estimated glomerular filtration rate (eGFR) was calculated using the re-expressed Modification of Diet in Renal Disease (MDRD) Study equation and compared to serum creatinine. We hypothesized that metformin is used in patients with undetected advanced CKD (i.e. serum creatinine is ≥1.5 mg/dl). A chi-squared test was used to compare per cent differences of metformin use across demographic variables and eGFR in the NHANES cohort.

At the University of Chicago Diabetes Center, 36 of 234 (15.3%) patients with an eGFR of <60 ml/min/1.73 m(2) were receiving metformin. Data from NHANES, age >18 years and eGFR <60 ml/min/1.73 m(2) showed that Blacks with advanced nephropathy were three times more likely to receive metformin.

We conclude that metformin utilization occurs with a higher frequency than predicted by serum creatinine in people with eGFR <60 ml/min/1.73 m(2) . Given the very low incidence of lactic acidosis, the recommendation should be changed to reflect eGFR cut-off values rather than serum creatinine.