According to the study published on Feb. 25, 2013 in the JAMA Internal Medicine journal, patients taking Januvia or Byetta were twice as likely as those who took other drugs to end up hospitalized with a potentially fatal inflammation of the pancreas known as pancreatitis. Pancreatic lesions and inflammation, research found, can be caused by the drugs. (See the Fierce Pharma story)

Pancreatitis can lead to more serious problems such as pancreatic cancer and kidney failure.

The oral medication Januvia (sitagliptin) and the injectable Byetta (exenatide) can both increase amounts of GLP-1, a hormone in the body that stimulates the pancreas to produce insulin. The pancreas also produces digestive enzymes that, if activated before leaving the pancreas, can literally digest organ tissue and cause inflammation, abdominal pain, fever, nausea.

Doctors are now calling for more research into how GLP-1 drugs work in the body.

“This is the first real study to give an estimate of what the risk is,” said Dr. Sonal Singh, the study’s author. “Until now we just had a few case reports. We really need to know more about these drugs, as pancreatitis is on the pathway to pancreatic cancer.”

Other doctors such as Aaron Cypress of Joslin Diabetes Center in Boston said the study results won’t change his patient treatments.  “For me personally,” Cypress told Reuters, “it’s not going to change my practice pattern in terms of stopping the drugs, but we may revisit whether you’re showing any of the risk factors.”

Pancreatitis currently affects roughly 3 in 1,000 diabetes patients. The new study indicates the number jumps to 6 in 1,000 for those taking Januvia or Byetta.

Merck maintains Januvia and Janumet – sitagliptin mixed with metformin – are safe and effective, despite the study. The company said it has reviewed preclinical, post-marketing safety data and told Bloomberg News it found “no compelling evidence of a causal relationship” between sitagliptin and pancreatitis or pancreatic cancer.

Bristol-Myers Squibb, makers of Byetta, responded similarly. Company spokesman Ken Dominski told Bloomberg News the company was confident in the safety profile of Byetta and Bydureon (a once-a-week formula of Byetta). Dominski also said the company, “[W]ill continue to monitor any post-marketing reports of acute pancreatitis.”

Lawsuits Filed

Meanwhile, a number of lawsuits have been filed against both Merck and Bristol-Myers, which bought Amylin, Byetta’s original manufacturer, in 2012. According to the FDA, data compiled by the Institute of Safe Medication Practices recorded hundreds of reports of acute and chronic pancreatitis attributed to Januvia and Byetta in 2011. People who took these drugs and were diagnosed with pancreatitis and pancreatic cancer filed lawsuits against the drugmakers.

The lawsuits typically claim the makers of Januva and Byetta failed to inform patients of the risks and marketed the drugs even when they knew the risks. More lawsuits are expected to be filed as reports of complications rise.

by Matthews & Associates