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Randomized Controlled Trial
. 2022 Dec 17;108(1):4-12.
doi: 10.1210/clinem/dgac549.

Liraglutide for Weight Management in Children and Adolescents With Prader-Willi Syndrome and Obesity

Gwenaëlle Diene  1 , Moris Angulo  2 , Paula M Hale  3 , Cecilie H Jepsen  4 , Paul L Hofman  5 , Anita Hokken-Koelega  6 , Chethana Ramesh  7 , Serap Turan  8 , Maïthé Tauber  1   9
Affiliations
Randomized Controlled Trial

Liraglutide for Weight Management in Children and Adolescents With Prader-Willi Syndrome and Obesity

Gwenaëlle Diene et al. J Clin Endocrinol Metab. .

Abstract

Context: Prader-Willi syndrome (PWS) is characterized by lack of appetite control and hyperphagia, leading to obesity. Pharmacological options for weight management are needed.

Objective: To determine whether liraglutide treatment for weight management is superior to placebo/no treatment in pediatric individuals with PWS.

Methods: This was a multicenter, 52-week, placebo-controlled trial with a 16-week double-blinded period. Adolescents (n = 31, aged 12-17 years; Tanner stage 2-5) and children (n = 24, aged 6-11 years; Tanner stage <2) with PWS and obesity were included. Patients were randomized 2:1 to liraglutide 3.0 mg (or maximum-tolerated dose) or placebo for 16 weeks, after which placebo was stopped. Liraglutide was continued for 52 weeks. All patients followed a structured diet and exercise program throughout the trial. The coprimary endpoints were change in body mass index (BMI) standard deviation score (SDS) from baseline to 16 and 52 weeks. Secondary endpoints included other weight-related parameters, hyperphagia, and safety.

Results: Change in BMI SDS from baseline to weeks 16 and 52 was not significantly different between treatments in adolescents (estimated treatment difference: -0.07 at week 16 and -0.14 at week 52) and children (-0.06 and -0.07, respectively). Changes in other weight-related parameters between treatments were not significant. At week 52, hyperphagia total and drive scores were lower in adolescents treated with liraglutide vs no treatment. The most common adverse events with liraglutide were gastrointestinal disorders.

Conclusion: Although the coprimary endpoints were not met, changes in hyperphagia total and drive scores in adolescents warrant further studies on liraglutide in this population.

Keywords: BMI SDS; Prader–Willi Syndrome; adolescents; children; obesity; pediatric population.

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Conflict of interest statement

Conflict of Interest G.D. declares no conflicts of interest relevant to this publication. M.A. reports participation as a speaker for Novo Nordisk. P.L.H. has no conflicts of interest. P.M.H. and C.H.J. are employees and stockholders of Novo Nordisk. C.R. is an employee of Novo Nordisk. S.T. and A.H-K. declare no conflicts of interest relevant to this publication. M.T. has received fees for participating in scientific board meetings at Merck Serono, Millendo, Novo Nordisk, and Pfizer, has received a research grant from Pfizer, and holds 3 patents for oxytocin-related products in Prader–Willi syndrome.

Figures

Figure 1.
Figure 1.
Consolidated standards of reporting trials flowchart. aParticipants who permanently discontinued treatment but attended week 16 visit.
Figure 2.
Figure 2.
Change in BMI SDS in adolescents and children during the trial (full analysis set). Data are observed mean change in BMI SDS from baseline by treatment week for adolescents (A) and children (B) during the in-trial period. MI represents the estimated change in BMI SDS at week 16 and week 52 using an analysis of covariance model. Error bars are standard error of the mean. Abbreviations: BMI, body mass index; MI, multiple imputation; N, number of patients with available BMI SDS measurements; SDS, standard deviation score.
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Comment in

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