Metformin is widely considered to be the first-line drug of choice for type 2 diabetes, and its overall record of safety and efficacy is impressive. Unlike older classes of type 2 diabetes drugs, metformin doesn’t seem to raise the risk of hypoglycemia (low blood glucose), and it appears to actually improve the way your liver and cells throughout your body respond to insulin (either natural insulin from your pancreas or, for some people, injected insulin).
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But metformin has also experienced episodes of safety concerns, most recently when an analysis from the U.S. Food and Drug Administration (FDA) found low levels of a potentially cancer-causing contaminant called N-nitrosodimethylamine (NDMA) in batches of the drug from one manufacturer, as we noted in February. These levels were low enough that the agency said they pose essentially no danger, and are “similar to the levels you would expect to be exposed to if you ate foods like grilled or smoked meats,” according to an FDA statement.
The FDA analysis from February looked at formulations of the drug from seven different manufacturers, and the agency continued its testing procedures on other versions of metformin, which is a generic drug available from many different manufacturers in the Unites States. And now, based on its latest analysis, the agency has found troubling levels of NDMA that it says warrant a recall of certain versions of the drug.
As noted in an article on the recall request from Bloomberg, right now, the FDA is asking for a voluntary recall of metformin by five different manufacturers. These extended-release formulations are made by Amneal Pharmaceuticals Inc., Actavis Pharma Inc., Apotex Corp., Lupin Pharma and Marksans Pharma Ltd.
Apotex Corp. promptly issued an announcement that it was recalling all lots (batches) of its 500 milligram extended-release metformin, after the FDA notified the company that one lot was found to have elevated levels of NDMA. “Out of an abundance of caution, the company is extending the recall to all lots of Metformin Hydrochloride Extended-Release Tablets in the U.S.,” the announcement reads. “Apotex stopped selling this product in the US in February 2019, and there remains only limited product on the market.” No adverse events associated with the drug have been reported, the company notes.
According to the FDA, people who take metformin — any version, from any manufacturer — should keep taking the drug until they’ve talked with their doctor about the next steps in case they’re affected by a new recall. It’s impossible to estimate how many people who take metformin will be affected by the FDA’s new actions, but as the Bloomberg article notes, it’s estimated that only about a quarter of all U.S. metformin prescriptions are even for an extended-release version of the drug.
It’s important to note that the risk of NDMA contamination isn’t unique to metformin, or even related to the diabetes drugs specifically. NDMA can form due to flaws in the manufacturing process for different drugs, and has been found in drugs for high blood pressure and acid reflux. Metformin itself, the active ingredient, is not chemically related to NDMA, and there’s no reason to worry about NDMA contamination if you’re taking a version of metformin that hasn’t been singled out by the FDA.
The FDA’s investigation of potential NDMA contamination is ongoing, so it’s possible that versions of metformin from different manufacturers will be examined in the future and, if they contain unacceptable levels, recalled.
“As we have been doing since this impurity was first identified, we will communicate as new scientific information becomes available and will take further action, if appropriate,” said Patrizia
Cavazzoni, MD, acting director of the FDA’s Center for Drug Evaluation and Research, in a statement from the agency. “We understand that patients may have concerns about possible impurities in their medicines, and want to assure the public that we have been looking closely at this problem over many months in order to provide patients and healthcare professionals with clear and accurate answers.”