63 - Glucagon-like Peptide-1 Receptor Agonists - a Potential New Medication for Pediatric Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease in children in the US, rising alongside an increase in obesity and type 2 diabetes (T2DM). Left untreated, NAFLD leads to end stage liver disease, which is one of the leading causes for liver transplantation in adults. Adults with T2DM treated with glucagon-like peptide-1 receptor agonists (GLP-1 RA) have shown improvement in nonalcoholic steatohepatitis through improvement in insulin resistance, the common mechanism behind the development of NAFLD and T2DM. Currently, there are no medications available for the management of NAFLD or obesity in the pediatric population.

Objective:

We assess the effects of GLP-1 RA on markers of NAFLD and insulin resistance to address the critical, unmet need of a pharmacotherapeutic agent for pediatric NAFLD.

Design/Methods:

A total of 1312 pediatric patients from a T2DM clinic at a tertiary referral center were identified, with 15 meeting the following inclusion criteria: diagnosed with pre-diabetes or T2DM, prescribed a GLP-1 RA in the prior 12 months, with evidence of NAFLD indicated by elevation of alanine aminotransferase (ALT) to twice the upper limit of normal ( >50 for males, >44 for females). 6 patients were excluded for either never having started the medication, documentation of inconsistent use, or not having a follow up ALT. A total of 9 patients were included. Participants' ages ranged from 14 to 17. The average change between baseline and the first measurement after starting a GLP-1 RA was calculated for ALT, Hemoglobin A1c, and BMI.

Results: All patients had a decrease in ALT and A1c, and the most dramatic effect was seen within the first 180 days of starting the GLP-1 RA. ALT decreased by an average of 60% or 98 points within an average of 109 days. A1c decreased by an average of 2.2 points within an average of 114 days. BMI decreased by an average of 5% or 2.4 points within an average of 105 days.

Conclusion(s):

This case series highlights the potential for GLP-1 RAs in the management of pediatric NAFLD, T2DM, and obesity. There was a greater reduction of ALT and A1c compared to BMI suggesting that improvement in NAFLD may be independent of weight loss. More randomized, placebo-controlled studies are needed to evaluate the effects of GLP-1 RA on these conditions in the pediatric population. Limitations to this case series include sample size, the presence of confounding variables (such as initiation of other T2DM medications near the start of the GLP-1 RA) and variations in time intervals between measurements for each patient.