The discovery of NDMA impurities in a common diabetes drug

Singapore’s Health Sciences Authority (HSA) has recalled three locally marketed metformin medicines after it was discovered that they contained N-nitrosodimethylamine (NDMA) impurities.

This follows the discovery of NDMA in angiotensin II receptor blockers in 2018 and ranitidine earlier this year. NDMA has been found to have carcinogenic properties and metformin is the most commonly used type II diabetes medicine in the world.

The HSA have stated that the risk posed by these three medicines is low, as they have only been on the market locally for a short period of time. However, the findings have led international regulators to begin evaluation of nationally distributed metformin.

The United States (US) Food and Drug Administration (FDA) will work with manufacturers to test samples of metformin sold in the US and will appropriately recommend a recall if abnormally high levels of NMDA are found. It is worth noting that levels of NDMA found in metformin in Singapore are within the range that is naturally occurring in some food and water.

The European Medicines Agency (EMA) have stated that they are also working with drug-makers to test metformin medicines distributed to the European Union (EU). The expedited testing of metformin medicines in the EU will fall under Article 5(3) procedure, which was originally introduced when reviewing ranitidine medicines last year. The Medicines and Healthcare products Regulatory Agency (MHRA) is working closely with the EMA to determine if any further action is required. Health Canada is also collecting samples from companies to conduct its own testing.

All regulators have advised patients that they should not stop taking their metformin drug without first discussing options with their health care provider, as the risks from not having adequate diabetes treatment outweigh any possible effects of the low levels of NDMA seen in Singapore.

The FDA, EMA, MHRA and Health Canada have all released statements regarding nitrosamines in metformin. Check back for any updates on this issue.