Do incretin-based therapies cause acute pancreatitis?

In 2007 a question was raised about the causal relationship between the first of the glucagon-like peptide 1 receptor agonists, exenatide, and pancreatitis, as postmarketing reports of pancreatitis in patients treated with this agent had been received by the Food and Drug Administration (FDA). There had been six reports of hemorrhagic pancreatitis, with two of the cases resulting in death. An update of the package insert for Byetta was mandated. Sitagliptin entered the market about a year and a half later, and now there are similar reports of acute pancreatitis. As the number of patients treated with these agents increases, is it uncovering a risk not appreciated in the premarket phase or just what should be expected from the population treated with these agents? To date, 88 cases of acute pancreatitis have been reported to the FDA in patients taking sitagliptin (Januvia/Janumet). Of these, two cases have been hemorrhagic or necrotizing pancreatitis. A revision of the package insert for sitagliptin has been made recently. An examination of available data should help shed light on whether the relation is likely causal or merely incidental.