(469) A Shocking Side Effect of Semaglutide: Suspected Semaglutide-Induced Necrotizing Pancreatitis

Introduction: Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), is widely used for the management of type 2 diabetes and has gained popularity for weight loss. It is known to cause gastrointestinal side effects but rarely pancreatitis. Here, we present a case of suspected semaglutide induced necrotizing pancreatitis leading to shock.

Description: A 44-year-old female with history of type II diabetes and recent uncomplicated cholecystectomy four weeks ago transferred from a rural center where she was admitted for nausea, vomiting, and cramping abdominal pain. Recent medication changes included initiation of semaglutide two weeks prior. She was alert, febrile to 100.9F, tachycardic, and hypotensive requiring norepinephrine. Initial workup revealed white blood cell count 12.35 10*3/uL, lipase 22,000 U/L, amylase 3,355 U/L, AST 642 U/L, ALT 947 U/L, alkaline phosphatase 292 U/L, total bilirubin 1.96 mg/dL, triglycerides 182, and lactic acid 2.3 mmol/L. A computed tomography (CT) abdomen revealed significant swelling and stranding around the pancreas and mildly dilated common bile duct without signs of obstruction. The patient denied alcohol abuse. Infectious work-up including blood and urine cultures, chest x-ray, and respiratory panel were negative. Repeat CT showed full-thickness pancreatic necrosis and extensive peripancreatic fluid. General surgery was consulted to evaluate for compartment syndrome, but supportive care was pursued. She improved over the next several days and was discharged with instructions to cease semaglutide.

Discussion: GLP-1s have commonly known gastrointestinal side effects including nausea, vomiting, diarrhea, and constipation. Although rare, several care reports associate GLP-1s causing acute pancreatitis. While current studies like the SUSTAIN-6 trial do not strongly support a link between the use of GLP-1 RAs and pancreatitis, given our patient’s history and timing of semaglutide initiation without evidence of bile duct obstruction, alcohol use, or hypertriglyceridemia, we believe her necrotizing pancreatitis was caused by semaglutide. With the increase in popularity of GLP-1 use for diabetes and weight-loss, recognition and understanding of adverse reactions, specifically those with high mortality such as in this case, is imperative.