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Metformin Warning & Labeling Changes

FDA press release; 2016 Apr 4

Publish date:

The US Food and Drug Administration (FDA) is requiring labeling changes regarding the recommendations for metformin-containing medicines for diabetes to expand metformin’s use in certain patients with reduced kidney function. The current labeling strongly recommends against use of metformin in some patients whose kidneys do not work normally.

After reviewing a number of medical studies, the FDA concluded that metformin can be used safely in patients with mild impairment in kidney function and in some patients with moderate impairment in kidney function and is requiring changes to the metformin labeling to reflect this new information while providing the following specific recommendations on the drug’s use in patients with mild to moderate kidney impairment:

• FDA recommends that healthcare professionals follow the latest recommendations when prescribing metformin-containing medicines to patients with impaired kidney function.

• Patients should talk to their health care professionals if they have any questions or concerns about taking metformin.

The labeling requirements on how and when kidney function is measured in patients receiving metformin will include:

• Before starting metformin, obtain the patient’s eGFR.

• Metformin is contraindicated in patients with an eGFR below 30 mL/minute/1.73 m2.

• Starting metformin in patients with an eGFR between 30 to 45 mL/minute/1.73 m2 is not recommended.

• Obtain an eGFR at least annually in all patients taking metformin.

• In patients taking metformin whose eGFR later falls below 45 mL/minute/1.73 m2, assess the benefits and risks of continuing treatment. Discontinue metformin if the patient’s eGFR later falls below 30 mL/minute/1.73 m2.

• Discontinue metformin at the time of or before an iodinated contrast imaging procedure in patients with an eGFR between 30-60 mL/minute/1.73 m2; in patients with a history of liver disease, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinated contrast.

Citation: US Food and Drug Administration. Metformin-containing drugs: Drug safety communication – revised warnings for certain patients with reduced kidney function. FDA Web site. April 8, 2016. http://www.fda.gov/safety/medwatch/safetyinformation/safetyalertsforhumanmedicalproducts/ucm494829.htm. Accessed April 11, 2016.

Commentary: For years metformin has been contraindicated in patients with renal failure due to concern about a higher incidence of lactic acidosis in patients with renal failure who are on metformin. This FDA revision of the dose label for products containing metformin is a welcome change. In December of 2014, a seminal paper critically looked at the evidence for the use of metformin in mild to moderate renal failure and concluded that, “Metformin levels generally remain within the therapeutic range and lactate concentrations are not substantially increased when used in patients with mild to moderate chronic kidney disease (estimated glomerular filtration rates, 30-60 mL/min per 1.73 m2).” The paper suggested that given the benefit of metformin to patients with diabetes, of whom up to one-quarter have some degree of renal failure, and the lack of evidence of harm, metformin should be able to be used in this group. The paper recommended dose adjustments of metformin with maximum total daily dose in patients with mild renal insufficiency (GFR 45-60) of 2000 mg per day and in patients with moderate renal insufficiency (GFR 30-35) not to initiate therapy but that one may continue metformin with maximum daily dose of 1000 mg daily.1 —Neil Skolnik, MD

1. Inzucchi SE, Lipska KJ, Mayo H, Bailey CJ, McGuire DK, et al. Metformin in patients with type 2 diabetes and kidney disease: A systematic review. JAMA. 2014;312(24):2668-2675. doi:10.1001/jama.2014.15298.

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