Can GLP-1 (Glucagon-like peptide-1) receptor agonists affect Liver Function Tests (LFTs)?

Effect of GLP-1 Receptor Agonists on Liver Function Tests

GLP-1 receptor agonists can affect liver function tests, primarily by improving them through reduction of hepatic steatosis and inflammation, with evidence showing decreased transaminase levels in patients with non-alcoholic fatty liver disease. 1

Beneficial Effects on Liver Function Tests

GLP-1 receptor agonists have demonstrated several positive effects on liver parameters:

• Reduction in transaminase levels: Meta-analyses confirm that GLP-1 RAs significantly decrease alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels 2
• Improvement in hepatic histology: The LEAN trial showed more frequent resolution of non-alcoholic steatohepatitis (NASH) with liraglutide treatment compared to placebo 1
• Decreased hepatic fat content: GLP-1 RAs significantly reduce intrahepatic adipose tissue, as well as subcutaneous and visceral adipose tissue 2
• Reduced liver fibrosis progression: Treatment with GLP-1 RAs is associated with less evidence of liver fibrosis progression compared to no treatment 3

Mechanisms of Liver Function Improvement

The improvement in liver function tests with GLP-1 receptor agonists occurs through multiple mechanisms:

1. Anti-inflammatory effects: GLP-1 RAs exert anti-inflammatory effects that help reduce hepatic inflammation 1
2. Weight loss: The 2-4 kg weight loss typically seen with these medications helps reduce hepatic fat accumulation 4
3. Improved lipid profiles: GLP-1 RAs decrease triglyceride levels and improve high-density lipoprotein levels 4
4. Direct hepatic effects: These medications directly decrease fatty degeneration of the liver and reduce the degree of liver fibrosis 5

Potential Adverse Hepatic Effects

While GLP-1 RAs generally improve liver function tests, there are some potential adverse hepatic effects to be aware of:

• Rare elevations in liver enzymes: FDA labeling for liraglutide notes postmarketing reports of elevations of liver enzymes 6
• Hyperbilirubinemia: Mildly elevated serum bilirubin concentrations (up to twice the upper limit of normal) occurred in 4.0% of liraglutide-treated patients compared to 2.1% of placebo-treated patients 6
• Cholestasis: Postmarketing reports include rare cases of cholestasis with GLP-1 RAs 6
• Gallbladder disorders: There is an increased risk of cholelithiasis and cholecystitis with GLP-1 RA use, which can indirectly affect liver function tests 6, 7

Clinical Implications and Monitoring

When using GLP-1 receptor agonists in patients with or at risk for liver disease:

• Monitor LFTs at baseline and periodically during treatment
• Consider GLP-1 RAs as potentially beneficial for patients with type 2 diabetes and NAFLD/NASH 2
• Be aware of the potential for rare hepatobiliary adverse effects, particularly in patients with pre-existing gallbladder disease
• Watch for signs of improvement in LFTs, which may be seen within 3-15 months of treatment initiation 3

Case Evidence

A case report of a 25-year-old woman with type 2 diabetes and NASH showed normalization of liver function tests after 46 weeks of liraglutide treatment, with repeat liver biopsy showing reduction in hepatic fat content and inflammatory cells 8.

Recent research suggests that GLP-1 RAs may even reduce the risk of hepatocellular carcinoma and hepatic decompensation in patients with type 2 diabetes 9, further supporting their beneficial effect on liver health.

In conclusion, while GLP-1 receptor agonists can affect liver function tests, the predominant effect is improvement rather than deterioration, making them potentially valuable therapeutic options for patients with both type 2 diabetes and liver disease.