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.

Table 2 Suggested baseline and follow-up assessment

Clinical scenario	Assessment
Baseline	Alcohol history; metabolic risk factors; body weight, body mass index and/or waist circumference; ALT, AST, platelet count, HbA1c, lipid profile, renal function, and FIB-4
Low FIB-4 and no clinical concerns	Continue metabolic treatment; repeat liver risk assessment periodically according to metabolic risk and local pathway
Indeterminate or high FIB-4	Perform second-line non-invasive testing: Transient elastography, ELF testing, or hepatology referral
During ongoing therapy	Body weight and body mass index; tolerability and gastrointestinal adverse effects; HbA1c and fasting lipids; ALT, AST, platelet count, FIB-4 trajectory; renal function and hydration risk
After meaningful weight loss	Reassess liver enzymes and fibrosis risk markers; avoid concluding that weight loss alone indicates fibrosis regression
Older adult or frailty risk	Assess nutritional intake, muscle strength or function when feasible, fall risk, medication burden, and need for resistance exercise and protein optimization
Advanced fibrosis or cirrhosis	HCC surveillance per guideline; portal hypertension assessment; nutrition and frailty monitoring; decompensation monitoring; transplant consideration when appropriate

FIB-4: Fibrosis-4 index; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; HbA1c: Glycated hemoglobin; ELF: Enhanced Liver Fibrosis test; HCC: Hepatocellular carcinoma.