GLP-1s improve ALT in pediatric MASLD, could be ‘powerful option’ for some patients

Key takeaways:

• Treatment with GLP-1s resulted in significant mean reductions in ALT by 23.4 U/L at 6 months and by 18.2 U/L overall.
• Children with type 2 diabetes had greater mean reduction in ALT vs. those with obesity.

SAN DIEGO — Treatment with glucagon-like peptide-1 receptor agonists significantly reduced alanine aminotransferase among children with metabolic dysfunction-associated steatotic liver disease, especially those with type 2 diabetes.

“MASLD is the most common chronic liver disease in children, the rates continue to rise and is the fastest growing indication for liver transplant specifically in young adults ,” Andrea M. Tou, MBBCh, BAO, a fellow in the department of gastroenterology, hepatology and nutrition at Children’s Hospital of Philadelphia, told Healio. “Unfortunately, there’s no FDA-approved treatment for it yet for children and adolescents.

“We know that lifestyle modifications are effective in treating pediatric MASLD, but with the growing rates of obesity and pediatric MASLD, just like in adults, it’s really hard to consistently implement in practice. That’s why we need more pharmacologic options to be used alongside lifestyle.”

With limited data on the use of GLP-1s in pediatric MASLD, Tou and mentor, Jennifer Panganiban, MD, attending gastroenterologist and director of the Non Alcoholic Fatty Liver Disease Program at Children's Hospital of Philadelphia, conducted a retrospective cohort study of patients aged younger than 21 years who started treatment with GLP-1s at Children’s Hospital of Philadelphia from Jan. 1, 2018, to Jan. 10, 2024.

The primary outcome was a reduction of at least 17 U/L in ALT, while secondary outcomes included change in BMI z-score, weight and serum markers of metabolic dysfunction-associated comorbidities. All outcomes were assessed at baseline, 6 months and end of treatment.

The cohort included 111 patients (median age at GLP-1 initiation, 15 years; 51% boys; 40% white), whose mean baseline ALT and BMI were 78.1 U/L and 43 kg/m², respectively. The mean treatment duration was 13 months, with semaglutide the most frequently prescribed.

Paired Wilcoxon signed-rank test analysis showed a significant mean reduction in ALT by 23.4 U/L at 6 months and by 18.2 U/L overall (P = .02 for both). Notably, among patients with an ALT more than 2-times the upper limit of normal, levels improved by 46.8 U/L (P = .01).

“ALT improved in our patient population at 6 months and posttreatment,” Tou said. “That was really significant because, according to current AASLD and EASL guidelines, improvement in at least 17 U/L is associated with histologic improvement of MASH.”

Further, when stratifying patients by indication for obesity (51%) vs. type 2 diabetes (49%), the researchers observed a greater mean reduction in ALT by 32.9 U/L among those with diabetes (P = .02).

Tou also reported a mean decrease in BMI z-score of 0.07 (P < .01), although there were no notable changes in weight loss or BMI. Significant improvements were noted in aspartate aminotransferase, HbA1c, gamma-glutamyl transferase and triglycerides.

“Hopefully in the future [these results] could help guide the use of GLP-1 for pediatric patients with MASH, with the indication of obesity and type 2 diabetes who have the greatest risk for progression,” Tou told Healio. “We know that it may not be indicated for every MASLD patient, but I think eventually, having multiple options, could be a really powerful option for some.”