S3261 Weight Loss, Unexpected Cost: GLP-1 Receptor Agonist-Associated Acalculous Cholecystitis

Introduction: GLP-1 receptor agonists (GLP-1 RAs) are widely used for diabetes and weight loss due to their effects on insulin secretion, gastric emptying, and appetite suppression. While gastrointestinal side effects are common, biliary complications such as cholelithiasis and cholecystitis are less frequently reported. Acalculous cholecystitis, an acute necroinflammatory disease of the gallbladder occurring in the absence of gallstones, is a particularly rare consequence of GLP-1 RA use. We present a case of acalculous cholecystitis in a patient on chronic tirzepatide, adding to growing evidence of GLP-1 RA–associated biliary disease in the absence of traditional risk factors. Case Description/Methods: A 56-year-old man with a past medical history of hypertension, hyperlipidemia and gout presented to the emergency department with 3 days of right upper quadrant abdominal pain, nausea, vomiting and fever. For the past year, the patient was taking tirzepatide 7.5 mg weekly for weight loss, stating that he experienced progressive abdominal discomfort since initiation. Abnormal vitals upon admission were body temperature 100.6 F and heart rate of 109. Abnormal lab values included white blood cells of 15.52, sodium 125. Computed tomography abdomen showed evidence of acalculous cholecystitis. Confirmatory HIDA scan returned positive for cholecystitis without choledocholithiasis. The patient was diagnosed with acalculous cholecystitis and underwent cholecystectomy without complications. Blood cultures indicated E. coli bacteremia for which the patient received IV Rocephin with oral antibiotics prescribed upon discharge. The patient was advised cessation of tirzepatide weekly injection until after follow-up with their primary care provider. Discussion: Due to decreased bowel motility caused by GLP-1 RA effects on myenteric neurons and vagus parasympathetic activity, commonly documented side effects of use include ileus, nausea, vomiting and altered oral metabolism. Less commonly documented effects from Phase 3 trials include pancreatitis, cholelithiasis and cholecystitis. Acalculous cholecystitis is an exceedingly rare consequence, described by only 2 other published case reports to date. This case contributes another example of this rare association and highlights the extended biliary risks with GLP-1 RA use. While the mechanism of interaction is currently unknown, GLP-1 RAs may inhibit peristalsis of the biliary ducts in a similar manner to the bowel, making users more prone to biliary stasis and acalculous cholecystitis.