Analysis of Crowdsourced Metformin Tablets from Individuals Reveals Widespread Contamination with N-Nitrosodimethylamine (NDMA) in the United States

Reports of metformin drug products contaminated with unacceptable levels of the probable human carcinogen N-Nitrosodimethylamine (NDMA) prompted a national sampling of post-market metformin drug products in early 2020. To broadly sample the United States market and minimize supply chain bias, metformin medication samples were crowdsourced directly from individuals across many states. 155 samples were received, and liquid chromatography-high resolution mass spectrometry tests for a panel of nitrosamines and N,N-Dimethylformamide (DMF) revealed significant levels of NDMA and DMF that relate to formulation. 49% of all medication samples contained detectable levels of NDMA and, when scaled to maximum daily tablet dose, 16% of all medication samples contained NDMA levels exceeding the United States Food and Drug Administration acceptable daily intake (ADI) limit. The highest NDMA detection from the tested samples was 748 ng per 500 mg tablet, which, when scaled to a common 2000 mg per day dosage regimen, is 31 times the ADI limit. The presence of N,N-Dimethylformamide (DMF) across 74% of the sampled metformin products is concerning given its same carcinogenicity categorization as NDMA and proposed role in formation of NDMA. Results underscore the need for continued surveillance of product quality, recalls of tainted medications, and investigation of metformin manufacturing practices.