46 of 128 metformin samples that Valisure tested exceeded the FDA daily acceptable limit for N-Nitrosodimethylamine (NDMA), a probable human carcinogen.

NEW HAVEN, CT – MAY 27, 2020 – In a first-of-its-kind study, Valisure posted the results from their testing of crowdsourced samples of the drug metformin, a widely prescribed medication used to control high blood sugar, and detected high levels of the probable human carcinogen, N,Nitrosodimethylamine (NDMA). The study was posted to medRxiv.org, the preprint server for health sciences.

The study’s objective was to test for NDMA in tablets of metformin that were sent directly from individuals around the United States to Valisure’s laboratory. The intention of this study was to evaluate the prevalence of contamination in metformin with the least possible bias by sourcing direct from individuals.

The United States Food and Drug Administration (FDA) had previously posted lab results on February 3, 2020, which evaluated metformin tablets from 7 companies and 16 batches, finding that all passed the FDA’s daily acceptable intake limit for NDMA. However, the FDA may have acquired the drug or medication samples through voluntary submission, which can introduce significant sampling bias.

To independently evaluate the state of metformin contamination, Valisure acquired 38 batches of metformin from 22 companies through its pharmacy’s distributors and filed an FDA Citizen Petition with the results on March 2, 2020. In Valisure’s FDA Citizen Petition, 42% of the batches analyzed (16 of 38) contained NDMA exceeding the FDA’s daily acceptable intake limit with the highest detected amount over 16 times the permissible limit.

Valisure’s analysis of its pharmacy batches significantly widened the net beyond the FDA’s original report and likely reduced the sampling bias but was still limited by the availability of the drug from Valisure’s medication distributors. Therefore, a direct-to-consumer crowdsourcing study was conducted and resulted in the evaluation of 128 samples of metformin medication from individuals located in 30 states.

The study summarizes the results in its abstract: “42% of all medication samples contained detectable levels of NDMA and, when scaled to maximum daily tablet dose, 36% of all medication samples contained NDMA levels exceeding the FDA daily acceptable intake limit. The highest NDMA detection from the tested samples was 1565 ng per tablet, which, when commonly taken four times a day, is 65 times the United States Food and Drug Administration (FDA) acceptable daily intake limit.  Results underscore the need for immediate product recalls of tainted medications and an overall investigation of metformin manufacturing practices.”

A link to the study at medRxiv is below:

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

Metformin is an oral diabetes medicine that helps control blood sugar levels in adults and adolescents with type 2 diabetes. More than 30 million people in the United States have diabetes, of which 90 to 95% are type 2. Metformin is the fourth-most prescribed drug in the U.S. with approximately 80 million prescriptions written in 2019.

“The presence of this carcinogen in metformin where multiple tablets can be taken daily and often for a lifetime diabetic condition, makes this finding particularly concerning,” said Deanna Akinbajo, PharmD, MPH, Chief Pharmacist of Valisure. “Furthermore, the increased prevalence of diabetes in adolescents and young adults strongly underscores the need for quick action to protect patients.”

The carcinogenic nature of nitrosamines, and specifically NDMA, has been extensively studied by the scientific community since the 1960s. The World Health Organization (WHO) and the International Agency for Research on Cancer (IARC) have classified NDMA as a Group 2A compound thereby defining it as “probably carcinogenic to humans.” FDA currently recognizes the danger of this compound and, as a result, has set strict daily acceptable intake limits and advised companies to recall medications like valsartan, losartan, and ranitidine that did not meet this standard.

“The data from this study adds to a growing body of evidence which strongly suggests that approximately 4 out of 10 Americans currently taking metformin are being exposed daily to unacceptable levels of NDMA, a probable human carcinogen,” stated David Light, Founder and CEO of Valisure. “These results indicate that contaminated batches of drugs are scattered and intermixed with clean ones throughout the American pharmaceutical supply chain. Clearly, much more needs to be done to protect American consumers from this potentially dangerous contamination in the U.S. drug supply. Independent analysis of medication is needed more than ever.”

The initial analysis of metformin by Valisure earlier this year was prompted by an individual patient who requested Valisure test their medication sample. Individual patients can send Valisure a sample of their prescription medications to be analyzed for the presence of common probable human carcinogens such as nitrosamines.

The graph below is a summary comparison of data from various companies selling metformin as analyzed and/or reported by FDA, Health Canada, Valisure’s FDA Citizen Petition and this  crowdsourced study.

Overall, directly comparing Valisure’s pharmacy data with the crowdsourced data shows significant alignment between the data sets where companies overlap in the two studies, with few exceptions. Of the 27 companies sampled in the crowdsourced study, 13 were previously analyzed from Valisure’s pharmacy batches and 14 were new. A total of 36 companies selling metformin have now been evaluated through Valisure’s laboratory. Of the 7 companies evaluated by the FDA, 5 have now been analyzed independently by pharmacy and crowdsourced samples, 1 only by pharmacy samples and 1 by neither.

Media Coverage:

Bloomberg: FDA Finds Carcinogen in Some Forms of Popular Diabetes Drug

New York Times: U.S. FDA Finds High Levels of Carcinogen in Diabetes Drug Metformin

Fierce Pharma: FDA finds likely carcinogen in common diabetes drug metformin. Will recalls follow?

Becker’s Hospital Review: FDA finds carcinogen in popular diabetes drug

BioPharma Dive: Contaminated diabetes drugs raise red flag for FDA oversight

Fierce Pharma: FDA pushes metformin recalls for 5 drugmakers after carcinogen contamination

Reuters: U.S. FDA finds high levels of carcinogen in diabetes drug metformin

People’s Pharmacy: ALERT | Metformin Carcinogen Contamination Confirmed!

Pharmacist.com: FDA finds carcinogen in some versions of popular diabetes drug

The Wall Street Journal: FDA Asks Five Companies to Recall Diabetes Drug Metformin

About Valisure

Valisure is an online pharmacy attached to an analytical laboratory and is the first and only pharmacy in America that chemically batch-validates every medication it sells. Valisure’s mission is to help ensure safety, quality, and transparency in the medications it delivers to consumers. In response to rising concerns about counterfeit medications, generics, and overseas manufacturing, Valisure’s team of Harvard- and Yale-trained scientists developed proprietary analytical technologies to screen out poor-quality batches. Every medication or supplement Valisure ships comes with a certificate of analysis listing important chemical properties of the samples analyzed at Valisure’s lab. Valisure has ISO 17025 accreditation and is DEA and FDA registered. For more information, please visit www.valisure.com and or follow @Valisure on Twitter.

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