Tirzepatide-Induced Liver Injury: A Rare Complication

Background/Objective: Tirzepatide is widely prescribed and generally considered safe.The objective of this report is to describe a patient with tirzepatide-induced liver injury and increase awareness of this rare complication. CasePresentation: A 60-year-old female with type 2 diabetes mellitus and obesity presented with epigastric pain 21 days after starting tirzepatide 2.5 mg weekly.She previously received semaglutide and liraglutide (total 7 years) without hepatotoxicity.Isolated right upper quadrant abdominal tenderness was present.Alanine transaminase and aspartate transferase rose from mildly elevated to 1562 U/L and 1466 (normal 0-35), respectively, in 24 hours, disproportionately vs. alkaline phosphatase and bilirubin.Abdominal/pelvic computed tomography showed mildly dilated common bile duct post cholecystectomy.Right upper quadrant ultrasound demonstrated fatty infiltration, confirmed by magnetic resonance cholangiopancreatography.Acute hepatitis panel, acetaminophen level, ceruloplasmin, liver/kidney microsome type 1 Ab, antimitochondrial antibody, alpha-1-antitrypsin, and AFP tumor marker were normal.Following drug discontinuation, liver enzymes normalized after 24 days.Home medications were resumed except for tirzepatide and aminotransferases remained normal at 3 months.Discussion: Presentations of tirzepatide-induced liver injury include asymptomatic elevation of aminotransferases, or nausea, vomiting, and abdominal pain, or although extremely rare, hepatic failure.Risk factors and pathogenesis are undetermined.Conclusion: This case documents hepatocellular injury specific to tirzepatide despite previous tolerance of GLP-1 RA therapy.Clinician awareness is important since initial symptoms may be mild and attributed to common gastrointestinal side effects associated with tirzepatide.Early diagnosis and J o u r n a l P r e -p r o o f drug discontinuation resulted in resolution.If unrecognized, although rare, severe hepatic dysfunction with associated complications can result.