MON-639 A Case of Acute Pancreatitis Induced by Semaglutide

Abstract Disclosure: H. Marasandra Ramesh: None. S. Anighoro: None. R. Subramani: None. D. Fabian: None. Introduction: Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is widely used to manage type 2 diabetes and obesity due to its benefits in glycemic control, appetite suppression, weight loss, and cardioprotection. However, its association with pancreatitis is rare. We present a case of semaglutide-induced acute pancreatitis in an elderly patient, emphasizing the importance of recognizing this potential adverse drug reaction. Case Presentation: A 93-year-old male with a medical history of type 2 diabetes mellitus, hypertension, atrial fibrillation with a pacemaker, chronic kidney disease (stage III), and diastolic heart failure presented with worsening epigastric pain radiating to the back for 2-3 days, accompanied by nausea, vomiting, and watery diarrhea. Symptoms began six months earlier, shortly after starting once-weekly subcutaneous semaglutide (2 mg).The patient denied smoking and reported minimal alcohol use. (1 glass of wine weekly). Physical examination was notable for epigastric tenderness. Laboratory studies revealed elevated lipase (1410 U/L) and abnormal liver enzymes (AST 626 U/L, ALT 875 U/L, ALP 127 U/L). A CT scan showed acute interstitial pancreatitis and a 2.2 cm cystic lesion in the pancreatic head. Further evaluation with endoscopic ultrasound was recommended, as MRI could not be done due to pacemaker incompatibility. Detailed history revealed a striking temporal correlation between the onset of epigastric pain and semaglutide initiation for diabetes management six months earlier. The correlation between symptom onset and semaglutide initiation strongly suggested drug-induced pancreatitis. Semaglutide was discontinued, and the patient’s symptoms improved with intravenous fluids and analgesia. He was discharged after four days with outpatient endocrinology follow-up. Conclusion: Drug-induced pancreatitis is a rare but important differential diagnosis in acute pancreatitis. This case highlights the need for vigilance in identifying temporal associations between new medications and symptoms. The Naranjo score of 4 classified semaglutide as a probable cause of this patient's pancreatitis. Proposed mechanisms include excessive GLP-1 receptor activation on pancreatic exocrine and islet cells, leading to ductal obstruction and inflammation. Clinicians should consider this adverse effect in patients presenting with pancreatitis during GLP-1 receptor agonist therapy, as early recognition and prompt discontinuation of the drug can improve outcomes. Presentation: Monday, July 14, 2025