Breakthrough Medical Treatments for Obesity and Diabetes Advance Care for Children with NAFLD

As a pediatric gastroenterologist and director of Cincinnati Children’s Steatohepatitis Center, Stavra Xanthakos, MD, MS, works with children and adolescents affected by nonalcoholic fatty liver disease (NAFLD), now the most common cause of chronic liver disease in children in the United States.

The number of young adults requiring liver transplants due to NAFLD is on the rise, likely due to rising obesity and earlier onset of NAFLD in children. To help the growing number of affected children, Xanthakos and her colleagues developed a dedicated multidisciplinary NAFLD program in 2008.

“Our primary goal is to identify NAFLD early, in particular the more severe form of the disease nonalcoholic steatohepatitis (NASH), and to start interventions to stabilize and hopefully reverse the condition completely,” Xanthakos says.

Focusing on building healthy eating habits and increasing daily activity remains the foundation of treatment for all children with NAFLD.

However, “we aren’t always getting the results needed to improve health for many kids, especially for those with severe obesity,” Xanthakos says. “The combination of all the environmental factors driving the obesity epidemic and our bodies’ tendency to resist losing weight often make it hard to get to a healthy weight and reverse diseases associated with excess weight gain.”

GLP-1 Agonists Help Children Eat Less, Lose Weight

The good news is that advancements in pharmacology are bringing new medicines to the forefront that can reduce excess weight and improve severe metabolic conditions, including type 2 diabetes and NASH. Glucagon-like peptide 1 (GLP-1) agonists are a new class of medicine that mimic the actions of a natural peptide hormone produced by cells in the gut that stimulates insulin release after eating. The GLP-1 hormone also plays a role in appetite suppression and reduces food intake.

Initially approved for use in adults with type 2 diabetes, GLP 1 agonists were approved for treatment of diabetes in children 10 to 17 years old in 2019. Newer studies in the last few years show that the GLP-1 medications are also very effective in achieving weight loss, even when diabetes is not present. In 2021, liraglutide 3mg daily was the first GLP1 agonist to be approved for use in children 12 and older with severe obesity.

“GLP1 agonists are one of the most exciting developments for the treatment of obesity in both adults and children, with very positive outcomes compared to other treatments,” Xanthakos says. “A much higher proportion of patients achieve a 5% or 10% body weight loss in clinical trials compared to placebo.”

In the last year, trials in adults with NAFLD have also shown that GLP1 agonists can help resolve NASH at much higher rates than placebo, which is welcome news to Xanthakos and her colleagues, given the current lack of effective pharmacotherapies for this liver disease.

Many children with NASH have severe obesity or diabetes and therefore qualify for treatment with liraglutide, or with additional GLP1 agonists, if diabetes is present.

“Now that these GLP1 medications are approved as a treatment for severe obesity and diabetes in children, we are starting to offer them to children with NASH who meet those criteria, when lifestyle modification alone is insufficient to achieve good health outcomes,” Xanthakos says.

Clinical trials to date show good safety of the medications. The main side effects are nausea, vomiting or diarrhea. Increasing the dose slowly can help build tolerance. Currently, nearly all GLP-1 medications require daily or weekly injections, which makes them less attractive to some patients. But oral GLP1 agonists have been developed for diabetes treatment and may be developed for obesity treatment, too.

However, because these medicines are new, they are not always covered by health insurance companies as a treatment for obesity.

“As evidence of safety and efficacy grows in children and adults with severe obesity, we hope these GLP-1 medications will become more accessible, including for children who develop severe NAFLD,” Xanthakos says.