Glucagon-like peptide-1 receptor agonists in pediatric metabolic dysfunction-associated steatotic liver disease

Abstract

Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading chronic liver disease in children. Treatment with glucagon-like-peptide-1 receptor agonists (GLP-1RAs) have shown resolution of steatohepatitis with improvement in fibrosis in adults, yet pediatric studies are extremely limited. This study evaluates the impact of GLP-1RAs on pediatric MASLD, using alanine aminotransferase (ALT) reduction as a marker of improved disease activity. Methods: We conducted a single-center retrospective study in patients ≤18 years old with a diagnosis of MASLD, who were prescribed a GLP-1RA from January 2, 2018 and January 10, 2024 at the Children's Hospital of Philadelphia. Data were collected at baseline, 6 months, and at end-of-treatment (EOT). Inclusion required MASLD diagnosis per new criteria, elevated baseline ALT, and paired ALT values at baseline and EOT. Results: Forty-two patients met inclusion criteria (mean age 15 years, 64% male, 55% White). ALT improved by a mean of 56 U/L at 6 months (p = 0.04), and by 37 U/L at EOT (p = 0.004). Patients prescribed a GLP-1RA for type 2 diabetes mellitus (T2DM) had greater reductions in ALT compared to those treated for obesity. Improvements were also observed in aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), glycated hemoglobin (HbA1C), and triglycerides. Body mass index (BMI) percentile and z-score showed no significant changes, but BMI stabilization was observed. Conclusion: This is the largest pediatric study on GLP-1RAs in MASLD to date. On a GLP-1RA, ALT significantly improved at 6 months and EOT, suggesting their role in improving disease activity. This should thus be considered as an adjunct to lifestyle modification in treating pediatric MASLD.