Because incretin mimetic drugs are designed to stimulate cells in the pancreas, concerns have been raised about the potential for the medications to have potentially adverse effects on the organ. In fact, a growing body of evidence has shown that this class of diabetes drugs may increase the risk of diabetes patients developing acute pancreatitis and pre-cancerous cells possibly leading to pancreatic cancer. This potential risk was enough to lead the U.S. Food and Drug Administration (FDA) to issue an incretin mimetic safety communication in 2013, warning about research suggesting “an increased risk of pancreatitis, or inflammation of the pancreas, and pre-cancerous cellular changes called pancreatic duct metaplasia in patients with type 2 diabetes treated with a class of drugs called incretin mimetics.” Prior to that 2013 FDA warning, the agency had previously warned the public about “postmarketing reports of acute pancreatitis, including fatal and serious nonfatal cases, associated with the use of the incretin mimetic drugs exenatide and sitagliptin.”

The potential link between incretin mimetic drugs and pancreatic cancer was discovered as early as 2009, when Peter Butler, an endocrinologist from the University of California, Los Angeles, published a series of studies questioning the safety of incretin mimetic drugs, which he found caused certain pancreatic cells to multiply. Based on his research, Butler concluded that incretin mimetic therapy may increase the cells of the pancreas and cause the growth of pre-cancerous lesions. In April 2013, the FDA began analyzing research from Johns Hopkins University School of Medicine suggesting that incretin mimetic drugs increase the risk of users suffering pancreatitis, pre-cancerous cellular changes and pancreatic cancer. One year later, both the FDA and the European Medicines Agency announced that all incretin drugs would be required to carry a warning label highlighting the potential risk of pancreatitis. More recently, in 2018, a study published by the American Diabetes Association reviewed data from more than 33,000 patients treated with incretin mimetics and more than 525,000 patients treated with other medications, and found that incretin mimetic therapy was associated with double the risk of pancreatic cancer.