FDA is to assess data linking type 2 diabetes drugs with pancreatitisBMJ 2013; 346 doi: http://dx.doi.org/10.1136/bmj.f1808 (Published 19 March 2013) Cite this as: BMJ 2013;346:f1808
The US Food and Drug Administration has taken the unusual stance of announcing that it will evaluate data provided to it by a group of unnamed independent researchers indicating that glucagon-like peptide-1 (GLP-1) based drugs used in type 2 diabetes could raise the risk of pancreatitis and precancerous pancreatic lesions.
According to the FDA’s statement the data indicate an increased risk of pancreatitis and cellular changes called pancreatic duct metaplasia in people with type 2 diabetes who are treated with the drugs, which are incretin mimetics.1 However, the FDA emphasized that it has not reached any new conclusions about the safety of the drugs, nor has it “concluded that the drugs may cause or contribute to the development of pancreatic cancer.”
The findings were based on the examination of a small number of pancreatic tissue specimens taken from patients after they died from unspecified causes. The FDA said that it had asked the researchers to describe the methods used to collect and study these specimens and to provide the tissue samples so that it could carry out its own investigation.
The FDA statement comes two weeks after a study published in JAMA Internal Medicine showed that the risk of acute pancreatitis in people who took the GLP-1 based drugs exenatide and sitagliptin was twice that in people who took other antidiabetes drugs—although the absolute increase in risk was small.2 3 The drugs already carry warnings about the potential risk of pancreatitis.
Studies have previously shown that the GLP-1 based treatments may cause pancreatic inflammation and focal proliferation in the exocrine pancreas in rodents. However, the data provided to the FDA—as outlined in the agency’s alert—seem to be the first to examine human pancreas samples after incretin treatment and to identify proliferative changes.
Companies contacted by the BMJ, including Novo Nordisk, Eli-Lilly, Boehringer Ingelheim, Sanofi, and Merck—all of which make or market GLP-1 based drugs—confirmed that they had not done any tests on human tissue samples.
However, a spokeswoman for Novo Nordisk told the BMJ that clinical studies had shown the efficacy and safety of another drug in the class, liraglutide, in people with type 2 diabetes. The company has recently announced results of a phase III trial of use of the drug for obesity.
A spokeswoman for Merck said that its pooled analysis of 14 000 participants (submitted for publication) showed no excess reported cases of pancreatitis or pancreatic cancer among patients treated with sitagliptin. However, she cautioned that the studies “were not designed or powered to identify or adjudicate events of pancreatitis or pancreatic cancer and do not allow for inference on the potential for long term effects.”
A spokeswoman for the European Medicines Agency told the BMJ that the agency had requested the full data that the investigators submitted to the FDA and that it was due to discuss the issue this week.
She said, “There is currently no change to the official recommendations on the use of these medicines. Rare cases of acute pancreatitis have been reported with these medicines and the EU SmPCs [the European Union’s summaries of product characteristics] contain relevant warnings.”
A European study is currently being carried out to assess the pancreatic safety of all blood glucose lowering agents, she added.
Cite this as: BMJ 2013;346:f1808