GLP-1 RECEPTOR AGONISTS HAVE A POTENTIAL TO IMPROVE DISEASE ACTIVTY IN PEDIATRIC METABOLIC-DYSFUNCTION ASSOCIATED STEATOTIC LIVER DISEASE

OBJECTIVES: Pediatric Metabolic-dysfunction Associated Steatotic Liver Disease (MASLD), formerly known as Non-Alcoholic Fatty Liver Disease (NAFLD) is characterized by hepatic steatosis with at least one risk factor indicative of cardiometabolic dysfunction. In adults, glucagon-like-peptide-1 receptor agonists (GLP1-RAs) have been used to not only treat Type 2 Diabetes Mellitus (T2DM) and induce weight loss, but also to promote histologic resolution of steatohepatitis. There is a paucity of studies evaluating the use of GLP1-RAs in pediatric MASLD. Our objective was to determine the effect of GLP1-RAs in pediatric patients with MASLD, by using an ALT reduction of ≥17 U/L as a marker of improved disease activity according to AASLD guidance.

METHODS: This is a single-center IRB approved retrospective study conducted on patients < 21 years old who were started on a GLP1-RA at the Children’s Hospital of Philadelphia from 1/1/2018 – 5/20/2023, with a diagnosis code analogous to NAFLD / MASLD. Demographics and biometric data, start and end dates of each GLP1-RA medication, and transaminase values before and after treatment were obtained. Study endpoints included changes in ALT, Body Mass Index (BMI) Z-score and weight (kg) pre- versus post-GLP1-RA treatment. A Wilcoxon Signed Rank test assuming independent observations was used for statistical analysis.

RESULTS: 83 patients met our inclusion criteria. 40 were female, 43 were male. Ages ranged from 11-20 years old, with a mean age of 16. Liraglutide was the most prescribed GLP1-RA, followed by Semaglutide, Dulaglutide, and Exenatide. 42% of patients had been on > 1 GLP1-RA, without overlap. Mean treatment duration was 16 months. There was a significant mean reduction in ALT by 43 U/L (p < 0.002) post-GLP1-RA therapy. Mean BMI Z-score decreased only by 0.05 (p = 0.292). When stratifying for patients started on a GLP1-RA for the indication of obesity (59%) versus T2DM (41%), there was no observed improvement in BMI Z-score or weight. However, patients initiated on a GLP1-RA for T2DM had a greater change in ALT with a mean reduction by 50 U/L (p = 0.037), compared with patients initiated on treatment for obesity who saw a mean ALT reduction by 35 U/L (p = 0.112).

CONCLUSION: This is the largest dedicated pediatric study evaluating GLP1-RAs' effect on MASLD to date. Our results support the potential use of GLP1-RAs in the treatment of MASLD with the greatest impact in patients with T2DM. The mechanism by which this may occur does not seem exclusive to weight loss given no significant changes in BMI Z-score post-GLP1-RA initiation. This is hypothesized to be due to improvement in hepatic insulin resistance. Further data with standardization of medication dosing and duration, and evaluation of other biomarkers with imaging is required to better understand the impact of GLP1-RAs on the treatment of pediatric MASLD.