S3634 From Pancreatitis to Necrosis: A Severe and Rare Complication of Canagliflozin Use

Introduction: Acute necrotizing pancreatitis is most commonly attributed to alcohol use, gallstones, and metabolic disorders. While rare, sodium-glucose cotransporter 2 inhibitors (SGLT2i) use has been associated with acute pancreatitis. However, their association with necrotizing pancreatitis remains poorly established in the literature. We present a case of canagliflozin-induced acute pancreatitis that progressed to necrotizing pancreatitis, with the medication presumed to be the inciting factor after extensive workup. Case Description/Methods: A 76-year-old woman with a medical history of hypertension, type 2 diabetes mellitus on canagliflozin 100 mg, chronic kidney disease, Gilbert syndrome, and cholecystectomy presented with abdominal pain, nausea, and vomiting. She denied alcohol, tobacco use or recent trauma. On presentation, she was hypertensive and tachypneic with abdominal distension and epigastric tenderness. Laboratory workup was notable for leukocytosis, lactic acidosis, hyperglycemia, with lipase level over 4,000 U/L. Initial computed tomography suggested acute pancreatitis involving the pancreatic head, and no fluid collection. She was managed conservatively; however, her hospital course was complicated by ileus requiring nasogastric tube decompression. On hospitalization day 16, magnetic resonance cholangiopancreatography (MRCP) revealed necrosis involving the pancreatic head, body, and uncinate process, along with multiple fluid collections consistent with pseudocysts—the largest measuring 7.6 × 3.2 × 3.8 cm inferior to the uncinate process. Workup for alternate etiologies including choledocholithiasis, hypertriglyceridemia, and hypercalcemia was negative. IgG4 levels were within normal limits. Given the negative thorough evaluation for other causes, drug induced pancreatitis was concluded to be in the setting of canagliflozin. Twelve weeks later, the patient presented with diabetic ketoacidosis and chronic abdominal pain. Repeat abdominal computed tomography imaging revealed a walled off pancreatic necrosis measuring 7.13 cm in maximal diameter. Esophagogastroduodenoscopy ruled out gastric outlet obstruction. Discussion: Acute pancreatitis is a rare complication of SGLT2is. However, their association with necrotizing pancreatitis remains poorly characterized, with only 1 report in 2017, and it involved multiple potential other causative agents. We aim to highlight this potential side effect of canagliflozin-induced necrotizing pancreatitis, emphasizing the need for additional studies to better define this association.