Valisure Finds Unacceptably High Levels of NDMA in Metformin

The small Connecticut-based lab that first sounded the alarm about NDMA contamination in ranitidine (Zantac) is now issuing a similar warning over metformin, a commonly-prescribed, first-line treatment for type-2 diabetes. At the beginning of March, Valisure again filed a citizen's petition with the FDA urging a recall of lots determined to have NDMA contamination and to take additional action, including updating testing methods and keeping the public informed.

An analysis of metformin manufactured from 22 different sources found that half of the drug manufacturers and 16 out of 38 batches contained levels of NDMA above the “daily acceptable intake level” of 96 nanograms. Valisure reports that a number of the batches tested had more than ten times that limit, and the amount varied significantly between batches – even among those from the same drug company.

NDMA, or N-Nitrosodimethylamine, is part of a group of chemicals known as nitrosamines and has been identified by the World Health Organization as a probable human carcinogen. Concerns about NDMA contamination of prescription drugs first surfaced in 2018 when the substance was found in the active ingredient in valsartan, a common blood pressure medication of the ARB class. At that time, the source of the contamination was traced to a factory in China, which had made some changes to its manufacturing process that caused the formation of NDMA. Additional sources of NDMA contamination have been identified at facilities in India as well.

More recently, amounts of NDMA has been discovered in the popular antacid ranitidine, sold under the brand names Zantac and Wal-Zan. In October, Mylan Pharmaceuticals issued a recall for Xanax (alprazolam ), a common sedative and anti-anxiety drug, over contamination fears. The exact nature of the contamination was not specified, however.

Metformin, part of the biguanide class of diabetes medications, is based on a substance found in the French lilac (also known as “goat's rue”). It is generally well-tolerated, and serious side effects are rare. It is also the fourth most commonly prescribed medication in the world, and most patients wind up taking it for the duration of their lives. This makes Valisure's recent discovery of particular concern. According to chief pharmacist Dr. Deanna Akinbajo, “The increased prevalence of diabetes in adolescents and young adults strongly underscores the need for quick action to protect patients.”

Unfortunately, the FDA does not move quickly or aggressively when these dangers are brought to their attention. After Valisure announced its findings on ranitidine last fall, several countries took immediate action to pull affected products off of pharmacy shelves. Here at home, the FDA took another six weeks before it warned of “higher than acceptable levels” of NDMA in the batches that had been tested – then “requested” that drug companies issue their own voluntary recalls.

It appears that history will repeat itself. In early December, health authorities in Singapore took immediate action when three versions of metformin were found to be contaminated. In the U.S., the FDA did its own tests, and in February announced that the samples they tested either contained no NDMA or that it had been found only at “acceptably low levels.”