Liraglutide for non-alcoholic fatty liver disease in children and adolescents: has a new era arrived?

Liraglutide, an injectable glucagon-like peptide-1 receptor agonist (GLP-1RA), has been approved for use in adult patients with diabetes since 2010. There is an ongoing discussion regarding the potential role of liraglutide in the treatment of non-alcoholic fatty liver disease (NAFLD) in the paediatric population [1, 2]. To date, no solid evidence regarding any therapy of this disease exists, and thus no medication is currently recommended [3].
In the hallmark Liraglutide Efficacy and Action in NASH (LEAN) study, Armstrong et al. demonstrated that a significantly higher proportion of enrolled patients with non-alcoholic steatohepatitis (NASH) receiving liraglutide 1.8 mg daily, compared to those receiving placebo (relative risk (RR) = 4.5, 95% CI: 1.1–18.9), achieved the primary efficacy outcome, which was defined as the resolution of steatohepatitis (disappearance of hepatocyte ballooning) without worsening of fibrosis [4]. Concerning secondary efficacy outcomes, it was also shown that liraglutide induced a significant weight loss compared to placebo, equal to 4.39 kg [4]. Induction of delay in gastric emptying and increased satiation, as measured by maximum tolerated gastric volume, mediate the weight loss seen in patients treated with liraglutide [5]. A decrease in fasting hunger and energy intake and an increase in energy expenditure also characterise the liraglutide-induced weight loss [6].
The question that arises is whether liraglutide is a safe treatment option for paediatric patients. In a randomised, double-blind, placebo-controlled trial enrolling obese adolescents aged 12–17 years, Danne et al. demonstrated that there were no severe or serious treatment adverse events with liraglutide and no cases of treatment discontinuation, while liraglutide was effective, inducing an average weight loss equal to 2.55 kg [7]. However, there was a greater incidence of minor, symptomatic hypoglycaemic episodes and transient gastrointestinal adverse events among adolescents who were administered liraglutide. The pharmacokinetic profile was similar to that observed in adult patients [7]. Similar results were retrieved from another, recently published, randomised, double-blind, placebo-controlled trial enrolling obese children aged 7–11 years [8]. Mastrandrea et al. showed that liraglutide did not induce severe or serious adverse events, while it was more frequently associated with mild gastrointestinal adverse events. A few asymptomatic...


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