Tirzepatide (Mounjaro) and Elevated Liver Function Tests
Yes, tirzepatide (Mounjaro) can cause elevated liver function tests (LFTs), though this is a rare side effect that requires monitoring. 1
Evidence of Tirzepatide-Related Liver Effects
Recent evidence documents cases of tirzepatide-induced hepatotoxicity, though this adverse effect appears to be uncommon. A 2024 case report described a 37-year-old woman with metabolic syndrome who developed elevated liver enzymes specifically attributed to tirzepatide use 1. This represents one of the first documented cases of this specific adverse effect.
Mechanism and Presentation
The mechanism by which tirzepatide may cause LFT elevations is not fully established, but likely follows similar pathways as other medications that can cause drug-induced liver injury:
- Direct hepatotoxicity
- Immune-mediated mechanisms
- Metabolic effects on the liver
Elevated LFTs typically present as:
- Increased transaminases (AST/ALT)
- Possible elevation in alkaline phosphatase and bilirubin in more severe cases
Risk Assessment and Monitoring
While tirzepatide has been studied extensively for its benefits in type 2 diabetes and weight management 2, hepatotoxicity was not prominently reported in the SURPASS clinical trials 3. Interestingly, tirzepatide has actually been shown to have potential benefits for liver health in patients with metabolic dysfunction-associated steatohepatitis (MASH) 4.
However, given the documented case of hepatotoxicity, the following monitoring approach is recommended:
- Baseline LFTs: Obtain before initiating tirzepatide
- Regular monitoring: Check LFTs periodically during treatment, especially in the first 3-6 months
- Increased vigilance: Monitor more closely in patients with:
- Pre-existing liver disease
- Concomitant hepatotoxic medications
- History of drug-induced liver injury
Management of LFT Elevations
If LFT elevations occur during tirzepatide treatment:
- Mild elevations (<3× ULN): Continue monitoring LFTs every 1-2 weeks
- Moderate elevations (3-5× ULN): Consider dose reduction and more frequent monitoring
- Severe elevations (>5× ULN) or symptoms of liver injury: Discontinue tirzepatide and consult hepatology
Other Considerations
It's important to note that tirzepatide has been associated with other gastrointestinal adverse effects that are more common than hepatotoxicity:
- Nausea
- Vomiting
- Diarrhea
- Decreased appetite
Additionally, there is a documented case of tirzepatide-induced acute pancreatitis 5, which should be considered in the differential diagnosis when evaluating abdominal symptoms in patients taking this medication.
Conclusion
While tirzepatide offers significant benefits for glycemic control and weight management in type 2 diabetes, clinicians should be aware of the potential for elevated LFTs as a rare adverse effect. Appropriate monitoring and prompt management of any liver function abnormalities are essential to ensure patient safety while maximizing therapeutic benefits.