Is Metformin Safe for Patients with Kidney Disease?

Available data support the “cautious expansion” of metformin use for patients with type 2 diabetes and mild to moderate chronic kidney disease (CKD), according to a systematic review in the Journal of the American Medical Association.

A literature search identified 65 publications providing data on the risk of lactic acidosis in metformin-treated patients with impaired renal function. Since its approval in 1994, metformin has been contraindicated for use in patients with “renal disease or renal dysfunction.”

However, the evidence suggested that drug levels generally remained in the therapeutic range for metformin-treated patients with mild to moderate CKD (estimated GFR 30 to 60 mL/min/1.73 m2). Despite renal clearance of metformin, the rates of lactic acidosis were low and in the range of the background rate among all patients with diabetes: about three to ten cases per 100,000 person-years.

There were no randomized trials evaluating the safety of metformin in patients with impaired kidney function. Some reports suggested that the guidelines regarding metformin use in kidney disease are “commonly disregarded,” with no increase in adverse events. Observational studies suggested beneficial effects on macrovascular outcomes, even in patients with contraindications to metformin use.

On the basis of these data, the authors suggest a change in prescribing guidelines to permit metformin use in patients with mild to moderate CKD. They emphasize that any such strategy would require appropriate dosage reductions and careful monitoring of kidney function [Inzucchi SE, et al. Metformin in patients with type 2 diabetes and kidney disease: a systematic review. JAMA 2014; 312: 2668–2675].