GLP-1 Receptor Agonists and Liver Function Tests
GLP-1 receptor agonists can cause mild elevations in liver function tests, particularly bilirubin, but do not typically cause clinically significant hepatotoxicity and may actually improve liver health in patients with fatty liver disease. 1
Effects on Liver Function Tests
GLP-1 receptor agonists have been associated with:
- Mild bilirubin elevations: In glycemic control trials, mildly elevated serum bilirubin (up to twice the upper limit of normal) occurred in 4.0% of liraglutide-treated patients compared to 2.1% of placebo-treated patients 1
- Postmarketing reports: Elevations of liver enzymes, hyperbilirubinemia, and cholestasis have been reported 1
- Gallbladder disorders: GLP-1 RAs are associated with increased risk of cholelithiasis and cholecystitis, which can secondarily affect liver function tests 1
Beneficial Effects on Liver Health
Interestingly, GLP-1 receptor agonists have demonstrated beneficial effects on liver health:
- Reduced hepatic steatosis and inflammation: GLP-1 RAs show promise in reducing hepatic fat and steatosis 2
- Improved NASH outcomes: The LEAN trial showed more frequent resolution of non-alcoholic steatohepatitis (NASH) with liraglutide (9/23 vs 2/22; p=0.019) and less progression of fibrosis (2/23 vs 8/22; p=0.04) 2
- Decreased fibrosis progression: Recent research shows that patients treated with GLP-1 RAs had less evidence of liver fibrosis progression compared to untreated controls 3
- Reduced risk of hepatocellular carcinoma: GLP-1 RAs are associated with a lower risk of incident hepatocellular carcinoma compared with other anti-diabetes medications 4
Monitoring and Management
When using GLP-1 receptor agonists:
- Baseline liver function tests should be obtained before initiating therapy
- Periodic monitoring of liver function tests is reasonable, especially in patients with pre-existing liver disease
- Continue therapy despite mild elevations in liver enzymes or bilirubin if no other signs of liver injury are present
- Consider discontinuation if significant elevations occur or if signs/symptoms of liver injury develop
Special Considerations
- Patients with NAFLD/NASH: GLP-1 RAs may be particularly beneficial in these patients, as they can improve liver histology and reduce fibrosis 5
- Perioperative management: Current guidelines recommend continuing GLP-1 RAs throughout the perioperative period 6
- Heart failure patients: Use GLP-1 RAs with caution in patients with established heart failure with reduced ejection fraction (HFrEF) due to no evidence of benefit and a trend toward worse outcomes in small RCTs 6
Conclusion
While GLP-1 receptor agonists may cause mild elevations in liver function tests, particularly bilirubin, these changes are typically not clinically significant. In fact, these medications appear to have beneficial effects on liver health, especially in patients with fatty liver disease. Regular monitoring of liver function tests is reasonable, but mild elevations alone should not necessarily prompt discontinuation of therapy.