Tirzepatide-Induced Liver Injury: A Rare Complication

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.

A 60-year-old woman 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 U/L (normal 0-35 U/L), respectively, in 24 hours, disproportionately versus alkaline phosphatase and bilirubin. Abdominal/pelvic computed tomography scan showed a 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, α-1-antitrypsin, and alpha-fetoprotein 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.

Presentations of tirzepatide-induced liver injury include asymptomatic elevation of aminotransferases, nausea, vomiting, and abdominal pain, or, although extremely rare, hepatic failure. Risk factors and pathogenesis are undetermined.

This case documents hepatocellular injury specific to tirzepatide despite previous tolerance of glucagon-like peptide-1 receptor agonist therapy. Clinician awareness is important since initial symptoms may be mild and attributed to common gastrointestinal side effects associated with tirzepatide. Early diagnosis and drug discontinuation resulted in resolution. If unrecognized, although rare, severe hepatic dysfunction with associated complications can result.