EU to Review Metformin Meds to Unify Renal Recommendations

February 01, 2016

The European Medicines Agency (EMA) has begun a review of all metformin-containing medicines, which are widely used for treating type 2 diabetes, to look at recommendations on how they are used in patients with moderate renal impairment.

This follows a request from the Dutch medicines agency, the Medicines Evaluation Board (MEB), which conducted a routine safety evaluation that indicated the prescribing information for metformin-containing medicines varies between products and EU countries on this issue.

Prescribing information for metformin usually states that the drug is contraindicated in patients with renal impairment, because it has been associated, rarely, with lactic acidosis. Patients with reduced renal function are at higher risk of developing this serious adverse effect because their kidneys are unable to excrete as much lactic acid as those with normal renal function.

But the Dutch MEB is now questioning this, saying the results of its evaluation indicate that metformin may be of benefit in patients with moderate renal impairment; it is requesting that the EMA review this issue and harmonize the advice with regard to metformin-containing products across the European Union.

Are Patients With Moderate Renal Impairment Missing out on Metformin?

The issue of whether metformin is being underprescribed in patients with type 2 diabetes because of unwarranted concerns about its use in those with mild to moderate renal insufficiency is not new, and recommendations on the use of metformin in those with renal impairment differ around the world

For example, despite recommendations that metformin should be first-line therapy for type 2 diabetes, about half of patients in the United States are not prescribed it due in large part to the contraindication for use in renal impairment listed in the metformin labeling there.

The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) have addressed this issue as part of a joint position statement published last year (Diabetes Care. 2015;38:140-149), which cites "increasing evidence that the current cutoff points for renal safety [for metformin]…may be overly restrictive."

In its assessment, the Dutch MEB also concluded that the current scientific evidence might not justify contraindicating metformin in patients with moderate reduction of kidney function.

"This large group of patients may stand to benefit from treatment with metformin," says the EMA.

It also notes that the recommendations in the prescribing information for metformin "are often inconsistent with clinical guidelines on the treatment of diabetes."

The EMA will now review the data on the different metformin medicines and consider how the prescribing information for these medicines should be updated. In due course, it will issue an opinion on the marketing authorizations of these medicines across the European Union.


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