Liraglutide does not induce greater weight loss in youths with Prader-Willi syndrome
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Once-daily liraglutide was not associated with greater weight loss for youths with obesity and Prader-Willi syndrome compared with placebo, according to a study published in The Journal of Clinical Endocrinology & Metabolism.
“In our trial, BMI standard deviation score was reduced from baseline in both children and adolescents, but was not significantly different between liraglutide and placebo at week 16 or with no treatment at week 52,” Maïthé Tauber, MD, professor of pediatrics at the children’s hospital at University Hospital Center of Toulouse in France, and colleagues wrote. “Consistent with the coprimary endpoint findings, no significant differences were seen between liraglutide and placebo/no treatment groups for other weight-related endpoints at 16 or 52 weeks.”
Researchers conducted a randomized, placebo-controlled trial with children aged 6 years and older with pubertal development of less than Tanner stage 2, and adolescents aged 12 to 17 years with pubertal development at Tanner stage 2 to 5, with genetically confirmed Prader-Willi syndrome and obesity. Participants were randomly assigned 2:1 to a daily dose of liraglutide 3 mg (Saxenda, Novo Nordisk) or placebo for a 16-week double-blind period. Liraglutide treatment began with a 0.6 mg dose and increased weekly until the target or maximum-tolerated dose was reached. From weeks 17 to 52, the liraglutide group continued receiving treatment while the placebo group received no treatment except for diet and exercise. Change in BMI standard deviation score from baseline to 16 weeks and baseline to 52 weeks was the primary efficacy endpoint. The percentage of participants achieving a BMI reduction of at least 5% or 10%, weight change and changes in vital signs glycemic parameters and fasting lipids were also analyzed. Participants also completed the Dykens 13-item hyperphagia questionnaire.
The study cohort included 32 adolescents, of whom 20 were randomly assigned to liraglutide and 12 to placebo, and 24 children, of whom 17 received liraglutide and seven received placebo.
There were no significant differences in BMI standard deviation score between the two groups from baseline to 16 weeks and from baseline to 52 weeks. The proportion of participants who had a 5% or greater reduction in BMI was also similar between the two groups. Very few participants in either group achieved a BMI reduction of at least 10%. Change in body weight from baseline to 16 and 52 weeks was also similar between the liraglutide and placebo groups.
“The lack of effect of liraglutide on reducing BMI standard deviation score in this population is not completely understood, but may be related to the underlying hypothalamic dysregulation that characterizes Prader-Willi syndrome, which may hinder the known effect of liraglutide on appetite centers in the hypothalamus,” the researchers wrote. “However, it should be noted that GLP-1 receptor agonist treatment has been shown to be efficacious in some patients with hypothalamic obesity due to hypothalamic damage, including in those with craniopharyngioma, suggesting GLP-1-induced weight loss may not require a functioning and intact hypothalamus.”
At 52 weeks, adolescents using liraglutide had greater reductions in hyperphagia total score (estimated treatment difference; –6.42; 95% CI, –11.4 to –1.45) and hyperphagia drive score (estimated treatment difference; –3.87; 95% CI, –7.45 to –0.3) compared with placebo. No other differences in vital signs, glycemic parameters or fasting lipids were observed.
Gastrointestinal disorders were the most common adverse events reported in the liraglutide group. Most events were mild or moderate in severity. Few serious adverse events were reported during the study.
“The safety profile of liraglutide in our trial was overall consistent with that observed in other populations,” the researchers wrote. “Further research is needed to investigate the potential of GLP-1 receptor agonists in Prader-Willi syndrome.”
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