S3236 Balancing Blame: Acute Pancreatitis in the Setting of Hypertriglyceridemia and GLP-1 Therapy

Introduction: Acute pancreatitis is a known complication of severe hypertriglyceridemia, especially when levels exceed 1,000 mg/dL. Glucagon-like peptide-1 (GLP-1) receptor agonists, including exenatide, have also been implicated in cases of drug-induced pancreatitis. In patients with overlapping risk factors, distinguishing the primary etiology is critical for management and recurrence prevention. Case Description/Methods: A 58-year-old nonalcoholic man with type 2 diabetes on exenatide presented with diffuse epigastric pain, chest discomfort, and bilateral hand cramping. Labs showed glucose 488 mg/dL, calcium 7.9 mg/dL, lipase 711 U/L, lactic acid 4.9 mmol/L, cholesterol 213 mg/dL, and triglycerides 1,558 mg/dL. UA showed moderate glucosuria and his toxicology screens were unremarkable. Computed tomography imaging showed no acute abnormalities, with a normal-appearing pancreas and gallbladder. Based on abdominal symptoms and elevated lipase, the patient was diagnosed with acute pancreatitis. Cramping resolved with calcium repletion. Despite being on exenatide for 10 months without adverse effects—and prior tolerance of dulaglutide and semaglutide—the medication was discontinued due to its possible association with pancreatitis. Hypertriglyceridemia was considered the primary etiology. The patient was treated with IV fluids and transitioned from oral agents to an insulin drip in the intensive care unit, which was continued until triglycerides were under 500 mg/dL. He was started on glargine and lispro for glycemic control, remained on his statin, and was initiated on a fibrate. He was discharged on a low-fat, high-fiber diet with gastroenterology follow-up. Discussion: This case showcases the challenges of managing pancreatitis in the setting of multiple potential triggers. Although exenatide had been well-tolerated prior, it was discontinued out of caution given its reported link to pancreatitis. The 2020 ACC Expert Consensus advises discontinuing GLP-1 agonists in patients who develop pancreatitis, even when other risk factors are present. This case emphasizes the need for clinicians to consider both probable and potential contributors when determining the safest and most effective management to prevent recurrence.