A Case of Exenatide-Induced Recurrent Pancreatitis Despite Withdrawl of Drug Therapy

Introduction: An increasing number of cases of Exenatide-Induced acute pancreatitis have been reported and the FDA has issued a warning regarding this potential side effect. However, we report a novel case of recurrent pancreatitis, despite the discontinuation of Exenatide, in the absence of other precipitating factors. We followed the case of a 50-year-old male with history of HTN, DM type 2 (previously on Metformin, NPH Insulin and Exenatide for 2 years) that presented with acute pancreatitis (based on clinical symptoms, lipase and amylase levels and CT findings). Common causes of pancreatitis, including alcohol, gallstones, hypertriglyceridemia, infectious etiologies, and other medications were excluded prior to establishing the diagnosis of Exenatide-induced pancreatitis. Exenatide was discontinued during the initial admission, and he was treated conservatively until symptoms resolved. This patient was followed over the course of 7 months and was found to have two subsequent admissions with pancreatitis, despite having discontinued Exenatide. He was re-admitted 2-3 weeks after his first admission with laboratory and radiologic evidence of necrotizing pancreatitis and a pseudocyst. The patient was treated conservatively with intravenous fluids, pain management and was kept NPO. Symptoms resolved within 2 days and the patient was discharged. Two months later he had a third episode of pancreatitis with stable pseudocyst, which was also treated conservatively. Again, other etiologies of pancreatitis were absent. Based on our literature search, about 40 cases of Exenatide-induced pancreatitis, 6 of which were necrotizing or hemorrhagic, have been reported to the U.S. Food and Drug Administration in post-marketing trials as of 2008. A subsequent study reported a >6-fold increase in the risk of pancreatitis with use of Exenatide. The mechanism of how Exenatide may predispose to pancreatitis is not clearly understood. Exenatide is a GLP-1 agonist; studies have demonstrated in animal models that GLP-1 mimetic therapy may cause pancreatic acinar inflammation with elevated serum lipase levels. The association between exenetide and acute pancreatitis is well known, however recurrance of pancreatitis despite withdrawl of therapy has not been documented. Here we present the first case of Exenatide induced recurrent pancreatitis after withdrawal of drug therapy. Since recurrent and chronic pancreatitis are known risk factors for pancreatic cancer, this validates the concern that the drug may increase risk of pancreatic cancer. Further studies are warranted corroborate this hypothesis.