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Regulatory Focus™ > News Articles > Concerns about Diabetes Medicines go Global as EMA Investigates New Safety Risks

Concerns about Diabetes Medicines go Global as EMA Investigates New Safety Risks

Posted 27 March 2013 | By Alexander Gaffney, RAC

EU regulators have announced that they, like their US counterparts, are reassessing the risks associated with a class of diabetes drugs (GLP-1 incretin mimetics) in light of their potential to cause pancreatitis and cancer.


FDA approved Byetta (exenatide), a GLP-1 injection intended to treat type-2 diabetes, in October 2007. By August 2008, it had received dozens of reports associating the drug with acute pancreatitis, and issued a warning to healthcare professionals saying some of these cases could potentially be severe. In particular, FDA said it had received six cases of hemorrhagic or necrotizing pancreatitis in patients taking Byetta, two of which were fatal.

By September 2009, FDA's concerns had spread to another class of drugs known as DPP-4 inhibitors, which include the diabetes drugs Januvia (sitagliptin) and Janumet (sitagliptin/metformin), which exhibited nearly identical trends to those seen in some Byetta patients.

In both cases (GLP-1 and DPP-4), FDA advised providers to be vigilant and aware of the signs and symptoms associated with pancreatitis, and to discontinue the drugs if pancreatitis is suspected.

In 2013, FDA once again issued a warning to healthcare providers, saying it had become aware of still more potential risks to patients taking GLP-1 and DPP-4 incretin mimetics, including a general increase in the risk of cancer.

While the risks of pancreatitis remained relatively stable, FDA said the list of drugs associated with those risks had grown to include exenatide (Byetta, Bydureon), liraglutide (Victoza), sitagliptin (Januvia, Janumet, Janumet XR, Juvisync), saxagliptin (Onglyza, Kombiglyze XR), alogliptin (Nesina, Kazano, Oseni), and linagliptin (Tradjenta, Jentadueto).

Based on what FDA called an "examination of a small number of pancreatic tissue specimens taken from patients after they died," it said it is concerned about "potential pancreatic toxicity" associated with the drugs. These associations are not yet conclusive, FDA added in its statement. Accordingly, the agency said it intends to study the issue in further depth and participate in a June 2013 meeting being run by the National Cancer Institute (NCI) on the association between pancreatitis, diabetes and pancreatic cancer.

EMA Voices Identical Concerns

Now the European Medicines Agency (EMA) has announced it will also begin its own investigation into the drugs in light of the increased risks of pancreatitis and precancerous cellular changes thought to be associated with them.

"The Agency's Committee for Medicinal Products for Human Use (CHMP) and Pharmacovigilance Risk Assessment Committee (PRAC) are currently investigating the information provided by the researchers to determine the need for possible further regulatory action," EMA said in a statement on 26 March 2013.

As with FDA, EMA said it has not yet reached any definitive findings, and said patients should not stop taking their medications without first consulting with their doctors.

Regulators said that they are also involved in a large-scale study, the SAFEGUARD Study, to collect safety data from diabetes medicines from around the EU. The estimated completion date of that study was not yet known, and EMA did not mention whether it would be mining that data to help make any risk or safety determinations regarding incretin mimetics.

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