Study Finds Type 2 Diabetes Drugs And Pancreatic Cancer Association

According to a study, two newer drugs used to treat type 2 diabetes could be linked to a significantly increased risk of developing pancreatitis and pancreatic cancer, and one could also be linked to an increased risk of thyroid cancer.
Researchers examined the U.S. Food and Drug Administration’s database for adverse events reported between 2004 and 2009 among patients using the type 2 diabetes drugs sitagliptin and exenatide. They found a six-fold increase in the odds ratio for reported cases of pancreatitis with these drugs, compared with four other diabetes therapies they used as controls. They also found that patients who took the two type 2 diabetes drugs were more likely to have developed pancreatic cancer than those who were treated with the other therapies.
“We undertook these studies because several studies in animal models by several investigators had suggested that this form of therapy may have unintended actions to promote growth of the ducts (tubes) in the pancreatic gland that convey digestive juices from the pancreas to the gut,” said study co-author Dr. Peter Butle. “This is a concern if it happens in humans since it might be expected to increase the risk for pancreatitis and pancreatic cancer. While the FDA data base has limitations, it does have advantages in being very large, openly accessible and independent from companies that market the type 2 diabetes drugs.
“Taken together the animals studies and the FDA data base analysis suggest that further work needs to be undertaken to at least rule out that this now widely available new type 2 diabetes drug class does not increase the risk of pancreatic cancer,” added Butler.
Sitagliptin and exenatide are type 2 diabetes drugs that enhance the actions of a gut hormone known as glucagon-like peptide 1 (GLP-1), which has been shown to be effective in lowering blood sugar in individuals with type 2 diabetes. Sitagliptin, marketed as Januvia by Merck & Co. Inc., works by inhibiting dipeptidyl peptidase-4 (DDP-4), an enzyme that degrades GLP-1. Exenatide, manufactured by Amylin Pharmaceuticals and sold as Byetta, mimics the action of GLP-1 and resists DDP-4 degradation.
Previous research suggested there might be a link between drugs that enhance the actions of GLP-1 and pancreatitis, possibly resulting from an increase in the rate of formation of cells that line the pancreatic ducts. That research, based on studies in rats, was published in 2009 in the journal Diabetes.
In addition to the six-fold increase in reported cases of pancreatitis, the researchers also found a 2.9-fold greater rate of pancreatic cancer in patients using exenatide and a 2.7-fold higher rate of pancreatic cancer in patients on sitagliptin, compared with the other therapies. Additionally, they found a statistically significant increase in the risk of thyroid cancer among the exenatide group, but not among the sitagliptin group.
The FDA data did not indicate links between the two type 2 diabetes drugs and any other form of cancer.
The researchers caution that the FDA’s adverse events database “is not the ideal mechanism to compare adverse event rates between type 2 diabetes drugs,” given its known limitations, such as incomplete data and reporting biases. They stress that more study is needed.