In May 2020, the Food and Drug Administration (FDA) released a statement regarding higher-than-acceptable levels of a substance called N-nitrosodimethylamine (NDMA) in some preparations of extended-release metformin.

Initially, two pharmaceutical companies—Amneal Pharmaceuticals and Apotex—were involved in the recall. The FDA then requested other drug manufacturers evaluate their products and test for NDMA. Subsequently, some lots of extended-release metformin from the companies of Marksans Pharma, Lupin, and Teva Pharmaceuticals were recalled as well.

What Is Metformin?

Metformin is a prescription medication used first-line to treat type 2 diabetes. It is prescribed frequently, with over 60 million prescriptions since 2012 in the United States. 

The goal of treating diabetes is to decrease the amount of glucose, or sugar, in the blood. Metformin works in a variety of ways to decrease glucose.

One way it works is by allowing muscle cells to use more glucose. The increased use of glucose by the muscles lowers the glucose level in the blood. In addition, metformin decreases the liver’s ability to make glucose and reduces the amount of glucose absorbed by the intestines. 

Metformin can also be used off-label to treat polycystic ovarian syndrome or as an aid to weight loss. 

Metformin is generally well tolerated; the most common side effects include:

  • DiarrheaNauseaVomitingAbdominal bloatingGas

What Is NDMA?

N-nitrosodimethylamine (NDMA) is a chemical that is formed naturally and is a byproduct of some manufacturing processes. Very low levels of NDMA can be found in chlorinated water, as well as in cured or smoked meats, and malt beverages such as beer or whiskey.

Metformin and Cancer

Cancer is not a reported side effect of metformin. In fact, the American Diabetes Association and the American Cancer Society have reported that metformin may be associated with a decreased risk of certain cancers, such as:

NDMA can also form during the drug manufacturing process or may form when medications are stored.

These studies showed that high levels of NDMA (10,000 nanograms/kg/day) in dogs, rats, and mice caused significant liver fibrosis and cirrhosis. These liver diseases then led to the development of liver cancer. There are no specific studies of the carcinogenic effect of NDMA directly on humans.

NDMA and Cancer

The International Agency for Research on Cancer (IARC) classifies NDMA as “probably carcinogenic to humans,” based on animal studies.

The Environmental Protection Agency limits on NDMA in water are 0.7 nanograms/L, far less than the amount found to cause cancer in rats.

Why Metformin Was Recalled

The FDA has investigated the levels of NDMA in metformin over the last few years because it was found to be elevated in some lots of metformin made outside of the United States. During their investigation, metformin products in the United States were found to be higher than the FDA daily allowance amount of 96 nanograms per day.

For example, the Apotex-manufactured metformin was found to have up to 90 nanograms of NDMA, and Amneal products were found to have up to 395 nanograms of NDMA. Only extended-release products were found to have unacceptable levels of NDMA, and no immediate-release formulations were recalled.

Also, not all manufacturers were affected, which means metformin can be manufactured without the presence of NDMA.

How Does NDMA Form?

Testing has shown that NDMA was found in the finished metformin tablets and not in samples of the active ingredients. This suggests that NDMA may develop at some point in the manufacturing process.

What You Should Do

Metformin is not the only medication that has been evaluated or recalled by the FDA for higher-than-acceptable levels of NDMA. In recent years, valsartan, a cholesterol-lowering medication, and ranitidine, a heartburn medication, were recalled and removed from the market due to NDMA. 

Unlike other medications—like ranitidine or valsartan, which have available alternatives—there is no substitute for metformin. If you are taking metformin and question if your medication has been recalled, specific details can be found on the FDA Drug Recalls list.

Recalled metformin medication should be taken to a pharmacy for proper disposal. 

A Word From Verywell

Overall, the risk of developing cancer from NDMA exposure is very low. However, if you are taking metformin and are concerned about this risk, you should discuss your concerns with your healthcare team. Don’t stop taking metformin until you’ve discussed it with your physician or another member of your healthcare team.

Speak with Your Doctor Before Stopping Any Medication

Do not stop taking metformin until first discussed with your healthcare provider, as discontinuation of diabetes treatment without another treatment in place may be dangerous.