PSUN270 Magnified Risk of Pancreatitis by GLP-1: A Case of Necrotizing Pancreatitis in a Patient on Dulaglutide with Baseline Elevated Triglycerides
Authors: Yau Alice , Reisman Tamar , Chen Zijian 
Published: November 2022

Abstract

Introduction
Glucagon-like peptide 1 receptor agonists (GLP-1 RA), used in the treatment of diabetes mellitus, have been associated with pancreatitis in both animal studies and clinical trials. Furthermore, GLP-1 RA are associated with increased levels of serum lipase and amylase, possibly indicating resultant pancreatic inflammation.1 While there is debate on the actual degree of risk of pancreatitis in patients on GLP-1 RA, there may be individuals who are at higher risk due to baseline comorbidities that may have their risk of pancreatitis further potentiated by treatment with GLP-1 RA. We present a case in which a patient with baseline moderately elevated triglycerides on long term GLP-1 RA develops necrotizing pancreatitis after minimal alcohol intake.

Case
A 46-year-old man with type 2 diabetes mellitus, hyperlipidemia, and depression presented with one day history of severe right upper quadrant abdominal pain, nausea, and non-bloody, non-bilious vomiting. He also endorsed subjective fevers and chills, shortness of breath, chest pain, and constipation. He reported that he had drank one bottle of sparkling wine the day prior but denied drinking regularly. Labs and imaging were consistent with acute necrotizing pancreatitis with elevated lipase (502 U/L), elevated triglycerides (TG) (3,480 mg/dL), and CT abdomen/pelvis showing focal hypoattenuation/edema of the pancreatic head with surrounding fat stranding. Subsequent MRI abdomen showed evolving necrotic pancreatitis with focal area of nonenhancement in the pancreatic head.
He denied any history of gallstones, recent trauma, diarrhea, weight loss, or prior pancreatitis. Review of his medications was notable for dulaglutide for management of his diabetes. He also had a history of consistently elevated TG to the mid-300s mg/dL as far back as 3 years ago.
Patient was ultimately managed conservatively with intravenous fluids with resolution of symptoms and downtrend of lipase and triglycerides. He was discharged on fenofibrate and icosapent ethyl for further triglyceride control.

Discussion
While several META analyses have not shown significant association between GLP-1 RA and pancreatitis, there still is a proportion of patients who have developed pancreatitis on GLP-1 RA.2 Our patient had baseline elevated triglycerides, but they were below the typical threshold for treatment. With minimal alcohol consumption, he still developed pancreatitis. We suspect that his risk for pancreatitis was magnified by his GLP-1 RA. We believe that in patients such as ours who have baseline independent risk factors for pancreatitis, GLP-1 RA should be carefully considered before initiation.
1. Trujillo J. Safety and tolerability of once-weekly GLP-1 receptor agonists in type 2 diabetes. J Clin Pharm Ther. 2020;45 Suppl 1(Suppl 1): 43-60. doi: 10.1111/jcpt.13225
2. Monami M, Dicembrini I, Nardini C, Fiordelli I, Mannucci E. Glucagon-like peptide-1 receptor agonists and pancreatitis: a meta-analysis of randomized clinical trials. Diabetes Res Clin Pract. 2014;103(2): 269-275. doi: 10.1016/j.diabres.2014.01.010
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