FDA evaluates diabetes drugs for possible increased risk of pancreatitis, precancerous cellular changes of pancreas

Diabetes drugs including exenatide (Byetta, Bydureon), liraglutide (Victoza), sitagliptin (Januvia, Janumet, Janumet XR, Juvisync), saxagliptin (Onglyza, Kombiglyze XR), alogliptin (Nesina, Kazano, Oseni), and linagliptin (Tradjenta, Jentadueto) are being evaluated by FDA for a potential link to pancreatitis and precancerous changes of the pancreas.

FDA is reviewing unpublished new findings by a group of academic researchers that suggest an increased risk of pancreatitis and precancerous cellular changes called pancreatic duct metaplasia in patients with type 2 diabetes treated with these incretin mimetics.

These findings were based on examination of a small number of pancreatic tissue specimens taken from patients after they died from unspecified causes. FDA has asked the researchers to provide the methodology used to collect and study these specimens and to provide the tissue samples so it can further investigate potential pancreatic toxicity associated with the incretin mimetics.

“The recent report of FDA’s review of the incretin mimetics and the potential contribution to pancreatitis and/or pancreatic cancer may serve as a cause for concern for many patients who are currently on these agents, so it is important for providers to inform patients that this review is still ongoing and there are currently no definitive conclusions,” Formulary advisor Abimbola Farinde, PharmD, MS, clinical staff pharmacist at Clear Lake Regional Medical Center, Webster, Texas, said.

“Providers should continue to closely monitor patients for any cellular changes in pancreatic tissue that may warrant an appropriate intervention,” Dr Farinde said.

It is not clear how significant this issue is, according to Formulary advisor James M. Wooten, PharmD, associate professor, department of medicine, section of clinical pharmacology, University of Missouri-Kansas City. 

“If researchers can determine a true link between these drugs and the development of pancreatitis and/or pancreatic cancer then the utilization of these drugs will be reduced significantly,” Dr Wooten said. “These side effects are quite severe and because this issue can affect mortality it would be difficult for physicians to prescribe these agents to their patients. What needs to be assessed is whether or not there is a true link; if there is a link, what is the potential risk to the patient. For example, the percentage that this side effect occurs; is this side effect dose related?; and finally, is this side effect reversible? Much of this data will take some time to compile.”

How incretin mimetics work

Incretin mimetics work by mimicking the incretin hormones that the body usually produces naturally to stimulate the release of insulin in response to a meal. They are used along with diet and exercise to lower blood sugar in adults with type 2 diabetes.

FDA will participate in the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and National Cancer Institute’s (NCI) Workshop on Pancreatitis-Diabetes-Pancreatic Cancer in June 2013 to gather and share additional information. FDA will communicate its final conclusions and recommendations when its review is complete or when it has additional information to report.

The Warnings and Precautions section of drug labels and patient Medication Guides for incretin mimetics contain warnings about the risk of acute pancreatitis. FDA has not previously communicated about the potential risk of precancerous findings of the pancreas with incretin mimetics. FDA has not concluded these drugs may cause or contribute to the development of pancreatic cancer.

For now, FDA advises that patients should continue to take their medicine as directed until they talk to their healthcare professional, and healthcare professionals should continue to follow the prescribing recommendations in the drug labels.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to FDA’s MedWatch Safety Information and Adverse Event Reporting Program.

• Complete and submit the report online: www.fda.gov/MedWatch/report.htm

• Download form or call (800) 332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to (800) FDA-0178.