Metformin is one of the most popular prescription drugs in the world, and it’s considered the first-line drug for type 2 diabetes. Since it was introduced to the U.S. market in the 1990s — after decades of use in Europe — metformin has transformed the treatment of type 2 by effectively replacing many of the older oral drugs that were previously used (and are still sometimes used). Unlike those drugs, metformin carries no increased risk of hypoglycemia (low blood glucose), and instead of causing weight gain, metformin is even associated with modest weight loss.
Originally introduced in the United States under the brand name Glucophage, metformin is now a generic drug that’s offered by many different manufacturers around the world. This means that even the same basic formulation — containing the same amount of the active drug — will vary slightly from manufacturer to manufacturer. And there are many different doses and formulations of metformin available, including both regular and extended-release versions.
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So when the recall of one version of metformin was first announced last year, it seemed reasonable to assume it would be a one-off event — that other metformin products wouldn’t be affected. Instead, 2020 turned out to be the year of (among other things) metformin recalls.
Concerns about possible carcinogen
As noted in an article at MedPage Today, the recent spate of metformin recalls actually began in December 2019, when the U.S. Food and Drug Administration (FDA) announced that it was investigating whether metformin products in the United States contained N-Nitrosodimethylamine (NDMA), an impurity that can be the result of processes used in pharmaceutical manufacturing. NDMA is known to cause changes in the genetic material inside cells, and as a result may increase the risk of certain types of cancer.
The FDA made this announcement after reports that metformin products sold outside the United States contained low levels of NDMA. Those levels, the FDA stated, fall within the range in which NDMA naturally occurs in certain foods – such as grilled or smoked meats. This doesn’t mean that NDMA is good for you, but it does put the risk posed by NDMA in prescription drugs in perspective. The FDA’s official acceptable daily intake limit for NDMA — which it uses to evaluate drugs — is 96 nanograms. This level, set in 2018, is based on a 1 in 100,000 risk of developing cancer after 70 years of exposure to NDMA.
Then, in February 2020, the FDA announced that its initial analyses had found trace amounts of NDMA in certain metformin products sold in the United States. At that time, though, it didn’t recommend any recalls or other corrective actions. But in May 2020, the agency announced that it had found NDMA levels in several extended-release metformin products to be higher than acceptable, and recommended that the manufacturers issue voluntary recalls. Those five manufacturers followed the recommendation and issued recalls of their affected products.
Following these initial recalls, the American Diabetes Association (ADA) issued a statement urging people who take metformin to “continue to take their metformin until their pharmacist supplies a different manufacturer’s product or their doctor prescribes a different treatment. Medications should not be stopped unless directed to do so by their doctor.”
More metformin recalls, and the outlook for 2021
Over the summer of 2020, the FDA announced further findings that prompted a second round of voluntary recalls for extended-release metformin, followed by more recalls in October and November. This brought the total number of recalled metformin products — all of them extended-release versions of the drug — to 254. This number includes different packaging variations of the same product — for example, a pack of 90, 100, or 500 tablets. A searchable list of all affected metformin products is available online from the FDA.
It’s important to note that all metformin recalls in 2020 were voluntary and issued out of an abundance of caution, and that none of the products were believed to pose an immediate safety risk. For that reason, there was never a recommendation to stop taking drugs you already have in your possession, or for doctors to change any prescriptions. As is often the case, many pharmacists switched to other versions of extended-release metformin when filling prescriptions.
But most people in the United States who take metformin weren’t affected in any way by the recalls of 2020, because extended-release metformin isn’t as common as simple immediate-release versions of the drug. If you do take extended-release metformin and are concerned about NDMA, you can talk to your pharmacist about the version of the drug you’re taking — but right now, none of the recalled products should be in distribution in the United States.
Or, if you’re especially concerned about NDMA, you can talk to your doctor about switching your prescription to an immediate-release version of metformin, since these formulations appear to be at a much lower risk for NDMA contamination.
Right now, there is every indication that the FDA will continue to test metformin products for NDMA, and to issue recall recommendations as appropriate based on these findings. No one knows if 2020 will turn out to be the year containing the peak of metformin recalls, or if even more recalls will follow this year. But so far, there’s no reason to believe that anyone taking metformin in the United States encountered any significant risk due to NDMA contamination — or that any such risk will be found going forward.