Liraglutide induces acute hepatocellular injury with positive rechallenge in a 58-year-old woman

Liraglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), is widely used for managing type 2 diabetes mellitus and obesity. While generally considered safe and effective for metabolic benefits, there are rare, idiosyncratic reports of liver injury. The mechanism behind such rare adverse events remains poorly understood, posing a challenge for clinicians in identifying at-risk patients and ensuring safe long-term use of GLP-1 therapies, despite their overall favorable safety profile compared to older antidiabetic drugs.

This case report details a 58-year-old obese woman with type 2 diabetes who developed acute hepatocellular injury after initiating liraglutide therapy. The patient's liver enzyme levels were monitored, and alternative causes for liver injury were systematically excluded. After initial drug discontinuation led to rapid improvement, a supervised rechallenge with liraglutide was performed to confirm causality. The RUCAM score (Roussel Uclaf Causality Assessment Method) was applied to evaluate the likelihood of drug-induced liver injury.

The patient developed marked hepatocellular injury 12 weeks after initiating liraglutide. Initial liver enzyme levels were significantly elevated, with alanine aminotransferase (ALT) 876 U/L and aspartate aminotransferase (AST) 702 U/L. Following liraglutide discontinuation, liver enzyme levels improved rapidly. A supervised rechallenge with liraglutide resulted in a recurrence of severe transaminitis within 10 days.

During rechallenge, ALT peaked at 1245 U/L and AST at 980 U/L, yielding a RUCAM score of 11, which strongly supports a highly probable drug-induced liver injury. This finding highlights a rare but definite idiosyncratic hepatocellular injury associated with liraglutide use.