New FDA Recommendations for Metformin Use in Patients With Reduced Renal Function

Jeffrey S. Berns, MD


May 20, 2016

Editorial Collaboration

Medscape &

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Hello. This is Jeffrey Berns, editor-in-chief of Medscape Nephrology. One of the bigger medical news items recently was the US Food and Drug Administration (FDA) change of the labeling for metformin and metformin-containing medications.[1]

The previous black box warning, which had been present since 1995, stated that metformin was contraindicated in men with a serum creatinine level above 1.5 mg/dL and women with a serum creatinine above 1.4 mg/dL. Many of us have thought that this warning prevented many patients from getting metformin who would benefit from it because we all know that the serum creatinine levels themselves can be predictive of a wide range of glomerular filtration rates (GFRs). Nevertheless, some people who had a GFR that should not preclude metformin use were excluded from getting it because of this black box warning.

I was actually surprised to learn that there are 18 metformin-containing medications on the market, and about 14.5 million patients per year in the United States receive metformin or metformin-containing medications. I won't go through all of the details of the new labeling, but suffice to say that rather than serum creatinine-based recommendations, they're now using estimated GFR (eGFR)-based recommendations. The major area of impact is that now patients who have an eGFR between 30 and 45 mL/min/1.73 m2 can continue to receive metformin or metformin-containing medications as long as there is an appropriate assessment of the risks and benefits of the therapy.

Of course everyone has been concerned about the risk for lactic acidosis with metformin (which is actually relatively rare), particularly in individuals with mild or moderate chronic kidney disease. What is not recommended as part of the new labeling is what some think is appropriate, which is a reduction in the dose of metformin by about 50% in those with an eGFR between 30 and 45 mL/min/1.73 m2.

The new labeling still indicates that metformin should not be used in patients who have an eGFR below 30 mL/min/1.73 m2, but it can be continued in those who start it while their eGFR is above 45 mL/min/1.73 m2. Interestingly enough, the new labeling doesn't recommend starting metformin in patients with an eGFR between 30 and 45 mL/min/1.73 m2. The label indicates that we should only start metformin at an eGFR above 45 mL/min/1.73 m2, continue it with assessment of the risks as it falls below 45 mL/min/1.73 m2, and then stop it altogether if and when the eGFR falls below 30 mL/min/1.73 m2.

There are other cautions about the use of contrast material and so forth that are not new. The good news from this—and I think it was a good move by the FDA—is that the new labeling will now allow access to metformin and metformin-containing medications to many people with diabetes who would benefit from this medication and were not able to receive it in a way that was consistent with the prior black box warning. This is good news, thanks to the FDA.

I'm Jeffrey Berns, editor-in-chief of Medscape Nephrology, from the Perelman School of Medicine at the University of Pennsylvania in Philadelphia. Thanks for listening.


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