Incretin-based therapies in hepatology practice

Table 1 Hepatology-relevant effects of glucagon-like peptide-1 receptor agonist and dual incretin therapy

Pathology	Potential benefit	Clinical uncertainty	Practical hepatology action
Obesity	Reduced hepatic fat and metabolic stress	Lean mass loss and frailty risk, particularly with rapid or unstructured caloric restriction	Monitor body composition risk; encourage protein intake and resistance exercise
Glycemic control	Reduced glucotoxicity and insulin resistance	Effect on fibrosis outcomes varies across agents and populations	Combine metabolic and fibrosis-based monitoring; do not rely on HbA1c alone
Steatohepatitis	Improved disease activity in histology-based trials	Durability and long-term clinical outcomes remain uncertain	Interpret histological and non-invasive test responses cautiously
Fibrosis	Signals of improvement with semaglutide, tirzepatide, and survodutide in selected non-cirrhotic populations	Fibrosis regression is less consistent than steatohepatitis resolution and may depend on disease stage	Use FIB-4 and elastography-based longitudinal follow-up
Cirrhosis	Possible metabolic benefit in selected patients	Limited histological efficacy in established compensated MASH cirrhosis	Continue standard cirrhosis care, HCC surveillance, and decompensation monitoring
HCC risk	Observational studies suggest possible risk reduction in some diabetic and MASLD populations	Findings are inconsistent and not sufficient to support chemoprevention claims	Maintain guideline-based HCC surveillance; treat HCC risk as unresolved
MASH pharmacotherapy	Potential complement to liver-directed drugs such as resmetirom	Optimal sequencing and combination therapy remain uncertain	Individualize according to fibrosis stage, metabolic indication, and local approval

MASH: Metabolic dysfunction-associated steatohepatitis; HCC: Hepatocellular carcinoma; MASLD: Metabolic dysfunction-associated steatotic liver disease; FIB-4: Fibrosis-4 index; HbA1c: Glycated hemoglobin.