Table of ContentsView AllTable of ContentsWhat Is Metformin?What Is NDMA?Why Metformin Was RecalledWhat You Should Do
Table of ContentsView All
View All
Table of Contents
What Is Metformin?
What Is NDMA?
Why Metformin Was Recalled
What You Should Do
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-releasemetformin.
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.
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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 treatingdiabetesis to decrease the amount of glucose, or sugar, in the blood. Metformin works in a variety of ways to decrease glucose.
Metformin can also be used off-label to treatpolycystic ovarian syndromeor as an aid to weight loss.
Metformin is generally well tolerated; the most common side effects include:
NDMA can also form during the drug manufacturing process or may form when medications are stored.
NDMA and CancerThe International Agency for Research on Cancer (IARC) classifies NDMA as “probably carcinogenic to humans,” based on animal studies.
NDMA and Cancer
The International Agency for Research on Cancer (IARC) classifies NDMA as “probably carcinogenic to humans,” based on animal studies.
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.
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.
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.
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.
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.
Also, not all manufacturers were affected, which means metformin can be manufactured without the presence of 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 theFDA Drug Recalls list.
Recalled metformin medication should be taken to a pharmacy for proper disposal.
Speak with Your Doctor Before Stopping Any MedicationDo not stop taking metformin until first discussed with your healthcare provider, as discontinuation of diabetes treatment without another treatment in place may be dangerous.
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.
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.
Correction-July 27, 2023:This article was updated to correct the indication for valsartan, which is used for lowering blood-pressure, not cholesterol.
8 SourcesVerywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.U.S. Food and Drug Administration.FDA updates and press announcements on NDMA in Metformin.Marshall SM.60 years of metformin use: a glance at the past and a look to the future.Diabetologia. 2017;60(9):1561-1565. doi:10.1007/s00125-017-4343-yU.S. Food and Drug Administration.Glucophage and Glucophage XR.Pottegård A, Kristensen KB, Ernst MT, Johansen NB, Quartarolo P, Hallas J.Use of N-nitrosodimethylamine (NDMA) contaminated valsartan products and risk of cancer: Danish nationwide cohort study.BMJ. 2018;362:k3851. doi10.1136/bmj.k3851George J, Tsuchishima M, Tsutsumi M.Molecular mechanisms in the pathogenesis of N -nitrosodimethylamine induced hepatic fibrosis.Cell Death & Disease. 2019;10(1):1-9. doi:10.3389/fimmu.2020.574276U.S. Food and Drug Administration.Laboratory tests metformin.Yang J, Marzan TA, Ye W, Sommers CD, Rodriguez JD, Keire DA.A cautionary tale: quantitative lc-hrms analytical procedures for the analysis of n-nitrosodimethylamine in metformin.AAPS J. 2020;22(4). doi:10.1208/s12248-020-00473-wU.S Food and Drug Administration.Drug recalls.
8 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.U.S. Food and Drug Administration.FDA updates and press announcements on NDMA in Metformin.Marshall SM.60 years of metformin use: a glance at the past and a look to the future.Diabetologia. 2017;60(9):1561-1565. doi:10.1007/s00125-017-4343-yU.S. Food and Drug Administration.Glucophage and Glucophage XR.Pottegård A, Kristensen KB, Ernst MT, Johansen NB, Quartarolo P, Hallas J.Use of N-nitrosodimethylamine (NDMA) contaminated valsartan products and risk of cancer: Danish nationwide cohort study.BMJ. 2018;362:k3851. doi10.1136/bmj.k3851George J, Tsuchishima M, Tsutsumi M.Molecular mechanisms in the pathogenesis of N -nitrosodimethylamine induced hepatic fibrosis.Cell Death & Disease. 2019;10(1):1-9. doi:10.3389/fimmu.2020.574276U.S. Food and Drug Administration.Laboratory tests metformin.Yang J, Marzan TA, Ye W, Sommers CD, Rodriguez JD, Keire DA.A cautionary tale: quantitative lc-hrms analytical procedures for the analysis of n-nitrosodimethylamine in metformin.AAPS J. 2020;22(4). doi:10.1208/s12248-020-00473-wU.S Food and Drug Administration.Drug recalls.
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
U.S. Food and Drug Administration.FDA updates and press announcements on NDMA in Metformin.Marshall SM.60 years of metformin use: a glance at the past and a look to the future.Diabetologia. 2017;60(9):1561-1565. doi:10.1007/s00125-017-4343-yU.S. Food and Drug Administration.Glucophage and Glucophage XR.Pottegård A, Kristensen KB, Ernst MT, Johansen NB, Quartarolo P, Hallas J.Use of N-nitrosodimethylamine (NDMA) contaminated valsartan products and risk of cancer: Danish nationwide cohort study.BMJ. 2018;362:k3851. doi10.1136/bmj.k3851George J, Tsuchishima M, Tsutsumi M.Molecular mechanisms in the pathogenesis of N -nitrosodimethylamine induced hepatic fibrosis.Cell Death & Disease. 2019;10(1):1-9. doi:10.3389/fimmu.2020.574276U.S. Food and Drug Administration.Laboratory tests metformin.Yang J, Marzan TA, Ye W, Sommers CD, Rodriguez JD, Keire DA.A cautionary tale: quantitative lc-hrms analytical procedures for the analysis of n-nitrosodimethylamine in metformin.AAPS J. 2020;22(4). doi:10.1208/s12248-020-00473-wU.S Food and Drug Administration.Drug recalls.
U.S. Food and Drug Administration.FDA updates and press announcements on NDMA in Metformin.
Marshall SM.60 years of metformin use: a glance at the past and a look to the future.Diabetologia. 2017;60(9):1561-1565. doi:10.1007/s00125-017-4343-y
U.S. Food and Drug Administration.Glucophage and Glucophage XR.
Pottegård A, Kristensen KB, Ernst MT, Johansen NB, Quartarolo P, Hallas J.Use of N-nitrosodimethylamine (NDMA) contaminated valsartan products and risk of cancer: Danish nationwide cohort study.BMJ. 2018;362:k3851. doi10.1136/bmj.k3851
George J, Tsuchishima M, Tsutsumi M.Molecular mechanisms in the pathogenesis of N -nitrosodimethylamine induced hepatic fibrosis.Cell Death & Disease. 2019;10(1):1-9. doi:10.3389/fimmu.2020.574276
U.S. Food and Drug Administration.Laboratory tests metformin.
Yang J, Marzan TA, Ye W, Sommers CD, Rodriguez JD, Keire DA.A cautionary tale: quantitative lc-hrms analytical procedures for the analysis of n-nitrosodimethylamine in metformin.AAPS J. 2020;22(4). doi:10.1208/s12248-020-00473-w
U.S Food and Drug Administration.Drug recalls.
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