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

GLP-1 Receptor Agonists Can Improve Liver Function Tests in Patients with NAFLD/NASH

GLP-1 receptor agonists can significantly improve liver function tests (LFTs) by reducing hepatic fat content and inflammation, particularly in patients with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH). 1

Mechanism of Action on Liver Function

GLP-1 receptor agonists affect liver function through several mechanisms:

• Reduction in hepatic steatosis: GLP-1 RAs decrease hepatic fat accumulation and steatosis 1
• Improvement in transaminase levels: They reduce circulating transaminase levels 1
• Anti-inflammatory effects: GLP-1 RAs decrease systemic inflammation, including reduction in CRP levels 2
• Histological improvement: They can lead to resolution of NASH without worsening fibrosis 2

Evidence of Liver Function Test Improvement

The impact of GLP-1 RAs on liver function tests is well-documented:

• In the LEAN trial, liraglutide showed more frequent resolution of NASH (9/23 versus 2/22; P=0.019) and less progression of fibrosis (2/23 versus 8/22; P=0.04) compared to placebo 1
• A meta-analysis of 16 randomized controlled trials (involving 2,178 patients) found that GLP-1 RAs significantly improved histologic resolution of NASH with no worsening of liver fibrosis (WMD: 4.08,95% CI 2.54-6.56, p<0.00001) 2
• GLP-1 RAs significantly reduced CRP levels (WMD: -0.41,95% CI -0.78 to -0.04, p=0.002) 2
• Among different GLP-1 RAs, semaglutide has shown the most robust evidence for benefit in patients with NASH and fibrosis 1

Clinical Applications in Liver Disease

GLP-1 RAs are particularly beneficial for:

• Patients with NAFLD/NASH: GLP-1 RAs can be used in patients with NASH, especially those with diabetes 1
• Patients with type 2 diabetes and chronic liver disease: A recent study showed that patients with chronic liver disease and type 2 diabetes who adhered to GLP-1 RA therapy had a 49% lower risk of major adverse liver outcomes (decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, or liver-related death) compared to non-users (RR=0.51,95% CI=0.14 to 0.88) 3

Safety Profile in Liver Disease

GLP-1 RAs have a favorable hepatic safety profile:

• Only mild changes in pharmacokinetic characteristics were observed in patients with different degrees of hepatic impairment 4
• No significant changes in liver enzymes were reported with GLP-1 RAs in clinical trials up to 2 years in length 4
• However, caution is recommended in patients with advanced cirrhosis due to limited clinical experience in these vulnerable patients 4

Potential Adverse Effects Related to Liver

While GLP-1 RAs generally improve liver function, some hepatobiliary adverse effects have been reported:

• Elevations of liver enzymes and hyperbilirubinemia (rare) 5
• Cholestasis (rare) 5
• Cholecystitis and cholelithiasis requiring cholecystectomy (uncommon) 5
• Hepatitis (rare) 5

Monitoring Recommendations

For patients starting GLP-1 RAs with known or suspected liver disease:

1. Obtain baseline LFTs before initiating therapy
2. Monitor LFTs periodically during treatment, especially in the first 3-6 months
3. Be vigilant for symptoms of gallbladder disease (right upper quadrant pain, nausea)
4. Consider dose adjustment in patients with severe hepatic impairment

Conclusion

GLP-1 receptor agonists not only improve glycemic control and promote weight loss but also have beneficial effects on liver function by reducing hepatic fat content, improving transaminase levels, and potentially resolving NASH. These agents represent a promising therapeutic option for patients with diabetes who have concurrent NAFLD/NASH.