We have been quite concerned about the most widely prescribed diabetes drug in the world. Metformin (Glucophage) is taken by over 18 million Americans. More than 90 million prescriptions are dispensed for this drug annually. There is growing evidence that a number of these formulations are contaminated with the nitrosamine NDMA (N-Nitrosodimethylamine). Now, the FDA admits that metformin carcinogen contamination is a problem.
Carcinogens In Our Medicines:
Many people may say that ignorance is bliss. We disagree. When it comes to potentially cancer-causing chemicals, we think people need to be informed so they can avoid taking unnecessary risks.
Valsartan, Losartan, Irbesartan:
We started reporting on carcinogen contamination of blood pressure medications called ARBs (angiotensin receptor blockers) during the summer of 2018. We were among the first to alert readers to problems with valsartan. A manufacturing company in China (Zhejiang Huahai Pharmaceutical) sold valsartan contaminated with the nitrosamine NDMA to a number of other drug companies.
Ultimately, nitrosamines were found in lots of valsartan formulations as well as in irbesartan and losartan. Dozens of generic drug companies had to pull over 1,000 ARB products off pharmacy shelves.
Then the popular heartburn medicine ranitidine (Zantac) was found to also have a nitrosamine issue. Thanks to an online pharmacy in New Haven, CT, called Valisure, the world was alerted to this problem.
Initially, the FDA downplayed the concern. We wrote extensively about our ranitidine concerns throughout the fall of 2019. Finally, on April 1, 2020, the agency announced that:
“FDA Requests Removal of All Ranitidine Products (Zantac) from the Market”
You can read about this sad saga of FDA delay at this link:
Ranitidine – Zantac is Going, Going Gone at Last!
Have you ever taken Zantac or ranitidine for acid stomach, indigestion or heartburn? Tens of millions of people did. Now, Zantac is going to disappear. Why?
Breaking News–Metformin Mess:
Questions about metformin carcinogen contamination arose at the end of last year. In December, 2019, Singapore pulled products that had unacceptably high levels of NDMA in metformin. Canada and Switzerland followed suit.
The FDA responded on December 5, 2019, with this statement:
“The FDA is aware that some metformin diabetes medicines in other countries were reported to have low levels of NDMA. Based on the information we have available, the levels of NDMA seen outside the U.S. are within the range that is naturally occurring in some foods and in water. While we are aware that some regulatory agencies outside the U.S. may be recalling some metformin drugs, there are no metformin recalls affecting the U.S. market at this time. The FDA is investigating whether metformin in the U.S. market contains NDMA, and whether it is above the acceptable daily intake limit of 96 nanograms. The agency will also work with companies to test samples of metformin sold in the U.S. and will recommend recalls as appropriate if high levels of NDMA are found.”
The message from the FDA boiled down to:
Keep taking your metformin. We’ve got you covered. We’re the FDA and we’ll protect you.
On February 3, 2020, the FDA reinforced that reassuring message. Its testing did not reveal worrisome metformin carcinogen contamination:
“The U.S. Food and Drug Administration posted laboratory results showing N- Nitrosodimethylamine (NDMA) levels in some metformin products approved in the U.S. FDA has determined that the levels of NDMA in metformin products tested range from not detectable to low levels. To date, no sample of metformin that FDA has tested exceeds the acceptable daily intake for NDMA. FDA has not recommended metformin recalls in the U.S.”
The FDA’s message:
Don’t worry, be happy metformin takers. The coast is clear.
Metformin Carcinogen Contamination:
A month later, though, the online pharmacy in New Haven, CT, reported that:
“Valisure’s analysis of 22 companies selling metformin and a total of 38 batches revealed 16 batches and 11 companies where NDMA levels were detected above the 96 nanograms (ng) daily acceptable intake limit. Several batches contained over 10 times the daily acceptable intake limit and there was significant variability from batch to batch, even within a single company. These findings underscore the importance of batch-level chemical analysis and the necessity of effective quality surveillance of medications.”
Valisure Reports New Metformin Carcinogen Contamination:
The Valisure online pharmacy just published a new report on metformin and nitrosamine contamination (medRxiv, May 26, 2020). Many People’s Pharmacy readers submitted samples of their metformin to Valisure for testing. Of the 128 samples that were analyzed, 42% “contained detectable levels of NDMA.”
The scariest findings:
“…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 New FDA Flip-Flop on Metformin Carcinogen Contamination:
One day after the Valisure results were published, the FDA notified Bloomberg that it had discovered NDMA beyond acceptable levels in some metformin formulations. At the time of this writing, the FDA has not announced recalls. A spokesperson for the agency told Bloomberg:
“‘We cannot confirm or deny a recall action before it has taken place,’ Peddicord said. The FDA ‘will continue to take quick and appropriate action when needed to protect American consumers.’”
A Rerun of Ranitidine?
If all this sounds vaguely familiar, it’s understandable. When Valisure notified the FDA that its testing of ranitidine had produced worrisome levels of the nitrosamine, the agency initially downplayed the problem. The official word was that levels were too low to do anything. Then the FDA flip-flopped and required a voluntary recall of virtually all the ranitidine heartburn medicine sold in the U.S.
When Valisure notified the FDA that its testing of metformin produced worrisome levels of the nitrosamine NDMA, the FDA responded again that levels were too low to be concerned. No action necessary. But now, we anticipate that the agency will start requesting voluntary recalls from a number of manufacturers within days.
What to Do About Metformin Carcinogen Contamination:
The FDA has no legal authority to initiate a mandatory recall of contaminated drugs. That comes as a shock to a lot of people. Most other regulatory agencies in Europe and other countries can recall any medicine that they conclude is dangerous. In the U.S., recalls are “voluntary.” Here is a link to this bizarre situation.
Stay alert for any FDA announcements about “voluntary” recalls. It may take your pharmacy several weeks (or months) to notify you if your metformin has been contaminated and is being recalled. If you learn that the manufacturer of your metformin is part of a recall, you can ask your pharmacist to substitute a product that has been tested and found to be OK.
Metformin that Passed Valisure’s Testing:
There is good news that many drug companies are capable of making metformin without NDMA. We worry that some of the problem products may have resulted from manufacturing shortcuts.
We have listed the metformin manufacturers that passed Valisure’s first batch testing analysis. You can find these companies at this link:
The most recent study from Valisure also lists companies that sold metformin with no detectable NDMA levels or with relatively low levels (below 96 ng). It will be interesting to see how Valisure’s data compare with the FDA’s results. You will find a preliminary comparison of FDA’s early analysis with Valisure’s investigation at this link. ]
Full disclosure: Valisure is advertising on The People’s Pharmacy podcast and daily newsletter. We have been advocating for years for more comprehensive product testing to ensure reliable quality of medications. Since the FDA does little if any testing itself, we are pleased that this online pharmacy has stepped forward to fill the gap. You can learn more at www.Valisure.com.
Learn more about a variety of strategies to keep blood sugar under control in our eGuide to Preventing & Treating Diabetes. Here is a link to our Health eGuides section. Share your thoughts about Metformin Carcinogen Contamination in the comment section below. Do you think the FDA has acted appropriately? We would love to get your perspective whatever it might be.