GLP-1 receptor agonists ‘have changed the playing field’ in pediatric MASLD

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Key takeaways:

  • Pediatric patients with MASLD experienced significant ALT reduction following treatment with GLP1-RAs.
  • This improvement was more “pronounced” for patients prescribed GLP1-RAs for type 2 diabetes vs. obesity.

WASHINGTON — Glucagon-like peptide-1 receptor agonists significantly reduced alanine aminotransferase levels in pediatric metabolic dysfunction-associated steatotic liver disease, especially those with type 2 diabetes, researchers reported.

“The study was prompted by my interest in the use of anti-obesity medications in the treatment of MASLD,” Jennifer A. Panganiban, MD, director of the Non-Alcoholic Fatty Liver Disease Program at Children’s Hospital of Philadelphia, told Healio. “Being trained in GI, nutrition and obesity medicine, I wanted to be able to offer my patients something in addition to lifestyle intervention and I knew this would be impactful.”

“GLP1-RAs have changed the playing field for our pediatric patients with MASLD. We have something more to offer if this medication is used wisely.” – Jennifer A. Panganiban, MD

In an earlier case series published in the Journal of Pediatric Gastroenterology and Nutrition, Panganiban and colleagues reported that liraglutide (Saxenda/Victoza, Novo Nordisk), in conjunction with lifestyle intervention, was effective in inducing and maintaining weight loss and improve insulin sensitivity among pediatric patients with metabolic dysfunction-associated steatohepatitis, overweight/obesity and type 2 diabetes.

“Since then, I’ve pushed for earlier use of GLP1-RAs in our patients who have not responded to lifestyle intervention alone and who have more advanced disease [with the goal] to prevent progression to fibrosis,” she said. “We know that up to 23% of patients who have fibrosis progress, so we can’t just watch and wait.”

To assess the use of GLP1-RAs in pediatric patients with MASLD, Panganiban and Andrea M. Tou, MBBCh, a fellow in the division of gastroenterology, hepatology and nutrition at Children’s Hospital of Philadelphia, conducted a retrospective study of patients aged younger than 21 years (n = 83; mean age, 16 years) who initiated therapy with GLP1-RA from January 1, 2018, to May 20, 2023.

The researchers collected demographics and biometric data, initiation and completion dates for each of the GLP1-RA medications, as well as transaminase values before and after treatment. Endpoints for the study included changes in ALT levels, BMI Z-score and weight prior to GLP1-RA treatment vs. after.

According to study results, although patients exhibited a significant mean reduction in ALT (–43 U/L; P < .002) following GLP1-RA treatment, the mean BMI Z-score only dropped by 0.05 (P = .292).

When the researchers stratified patients who initiated GLP1-RA treatment for obesity (59%) compared with diabetes (41%), they found no improvement in BMI Z-score or weight. However, patients with diabetes experienced a more significant reduction in ALT (–50 U/L; P = .037) vs. patients with obesity (–35 U/L; P = .112).

“What I find really interesting and unexpected is that our patients didn’t have significant weight loss, and the BMI Z-score and percentile were stable,” Panganiban said. “Despite this, there was improvement in ALT, which was more pronounced in our patients who were prescribed a GLP1-RA with the indication of diabetes. This tells me there is a mechanism aside from weight loss that drives this improvement.”

The researchers noted that 42% of patients had been on more than one GLP1-RA medication, without overlap, with liraglutide being most commonly prescribed, followed by semaglutide (Ozempic/Wegovy, Novo Nordisk), dulaglutide (Trulicity, Lilly) and exenatide (Bydureon, AstraZeneca).

They also reported that, based on these findings, additional prospective studies are needed to examine GLP1-RA use for pediatric MASLD and investigate the different mechanisms by which these medications affect the liver.

“When clinicians think of indications for GLP1-RA use in pediatrics, they primarily think of type 2 diabetes mellitus and obesity and goal for weight loss; I think the study shows the potential it has beyond weight loss and its role in the treatment of pediatric MASLD,” Panganiban told Healio. “GLP1-RAs have changed the playing field for our pediatric patients with MASLD. We have something more to offer if this medication is used wisely.”

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