Can patients with elevated liver enzymes take Glucagon-like peptide-1 (GLP-1) receptor agonists?

GLP-1 Receptor Agonists Are Safe and Potentially Beneficial for Patients with Elevated Liver Enzymes

GLP-1 receptor agonists can be safely used in patients with elevated liver enzymes and may actually provide liver benefits in those with metabolic dysfunction-associated steatotic liver disease (MASLD).

Safety Profile in Liver Disease

• GLP-1 receptor agonists (GLP-1 RAs) have minimal hepatic metabolism and do not require dose adjustment in patients with elevated liver enzymes 1
• These medications undergo primarily proteolytic degradation rather than hepatic metabolism, with most having renal excretion as their primary elimination pathway 2
• No significant changes in liver enzymes have been reported with GLP-1 RAs in clinical trials up to 2 years in length 1

Benefits in Liver Disease

GLP-1 RAs may actually provide significant benefits for patients with liver disease:

• They directly decrease fatty degeneration of the liver and reduce the degree of liver fibrosis 3
• 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) 3
• Recent evidence shows GLP-1 RAs are associated with a lower risk of progression to cirrhosis (HR 0.86; 95% CI, 0.75-0.98) in patients with MASLD and diabetes 4
• GLP-1 RAs are associated with reduced risk of incident hepatocellular carcinoma (HCC) compared to other anti-diabetes medications 5

Clinical Practice Guidelines

Current clinical guidelines support the use of GLP-1 RAs in patients with liver disease:

• The American Gastroenterological Association (AGA) clinical care pathway for NAFLD recommends that GLP-1 RAs can improve the cardiometabolic profile and reverse steatosis in patients with diabetes and NAFLD 2
• The AGA recommends that use of GLP-1 RAs in individuals with type 2 diabetes and NAFLD should be based on current American Diabetes Association guidelines 2
• Among available GLP-1 RAs, semaglutide has the best evidence of benefit in patients with NASH and fibrosis 2

Considerations for Specific Patient Populations

Patients with Advanced Liver Disease

• Caution is recommended in patients with advanced cirrhosis due to limited clinical experience in these vulnerable patients 1
• The protective association of GLP-1 RAs was not observed in patients with existing cirrhosis, suggesting greater benefit earlier in the disease course 4
• GLP-1 RAs are contraindicated in patients with Child-Pugh C cirrhosis and should be used with caution in Child-Pugh B cirrhosis 2

Dosing Considerations

• Gradual dose titration is recommended to minimize gastrointestinal adverse effects 2
• For semaglutide: start at 0.25 mg weekly for 4 weeks, then increase to 0.5 mg, 1.0 mg, and 1.7 mg weekly every 4 weeks until reaching the maintenance dose of 2.4 mg 2
• For liraglutide: start with 0.6 mg daily for 7 days, then increase to 1.2 mg, 1.8 mg, and 2.4 mg daily every 7 days until reaching the maintenance dose of 3.0 mg 2

Monitoring Recommendations

• Monitor liver enzymes periodically during treatment
• Pay attention to gastrointestinal symptoms, which are the most common adverse effects (nausea, vomiting, diarrhea) 3
• In patients with established heart failure with reduced ejection fraction (HFrEF), monitor closely for heart failure symptoms, including fatigue and exercise intolerance 3

Conclusion

GLP-1 receptor agonists are safe for patients with elevated liver enzymes and may provide significant liver benefits, particularly in those with MASLD. They should be considered as a treatment option for patients with diabetes and elevated liver enzymes, with appropriate monitoring and dose adjustments based on individual patient characteristics.