ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: N Engl J Med. 2020;382(22):2117–2128. doi: https://pubmed.ncbi.nlm.nih.gov/32233338/

Kelly et al. randomly assigned (1:1) n =251 obese adolescents (age 12 to <18 years) to receive either liraglutide (3.0 mg), a long-acting glucagon-like peptide-1 agonist, or placebo subcutaneously once daily in addition to lifestyle therapy. Liraglutide was superior to placebo in terms of reducing BMI z-score at week 56 from baseline (–0.22; 95% confidence interval –0.37 to –0.08). Liraglutide reduced BMI by –4.64 percentage points, and body weight by –4.50 kg, more than placebo. The most commonly reported adverse events were – as expected from clinical trials in adults – typical gastrointestinal side effects of GLP-1 analogue therapy (nausea, vomiting, diarrhea) which became less frequent over the course of treatment. Only very few participants in both groups had serious adverse events (n =3 vs. n =5).

The prevalence of obesity in children and adolescents has stabilized at a high level in recent years (1,2). The question of effective therapy strategies remains an important challenge with, among other factors, relevant health economic dimensions due to the high number of individuals affected.

Evidence-based guidelines for the treatment of obesity in children and adolescents recommend the implementation of multimodal lifestyle interventions with the aim of a long-term changes in dietary and exercise habits (3). However, the short- and medium-term changes in weight status that can be achieved with such therapy programs appear to be only small, both in clinical studies and under the conditions of regular medical care, and there is also a lack of data on desired (and possibly also undesired) long-term effects (4,5). Furthermore, the arsenal of available pharmacotherapeutic options for obesity in pediatric patients is more than limited, with no EMA-approved drugs in Europe, and only two FDA-approved substances (orlistat, phentermine) available in the US (6,7).

Although liraglutide treatment reduced BMI z -score and body weight, which are clinically meaningful according to current evidence (8), no significant change in any traditional cardiometabolic disease risk marker was observed between the intervention and placebo group. Therefore, more research is needed to develop risk-adapted, multi-modal treatment strategies for childhood and adolescent obesity. Given the here presented promising results and its overall good safety profile, liraglutide will hopefully find its place as a welcome addition to such tailor-made intervention approaches.

References:

1. Wabitsch M, Moss A, Kromeyer-Hauschild K. Unexpected plateauing of childhood obesity rates in developed countries. BMC Med. 2014;12:17. doi: 10.1186/1741-7015-12-17.

2. Ogden CL, Carroll MD, Lawman HG, Fryar CD, Kruszon-Moran D, Kit BK, Flegal KM. Trends in Obesity Prevalence Among Children and Adolescents in the United States, 1988–1994 Through 2013–2014. JAMA 2016;315:2292–2299.

3. Styne DM, Arslanian SA, Connor EL, Farooqi,IS, Murad MH, Silverstein JH, Yanovski JA. Pediatric Obesity—Assessment, Treatment, and Prevention: An Endocrine Society Clinical Practice Guideline. JCEM 2017;102 (3):709–757, https://doi.org/10.1210/jc.2016–2573">10.1210/jc.2016–2573.

4. Al-Khudairy L, Loveman E, Colquitt JL, Mead E, Johnson RE, Fraser H, Olajide J, Murphy M, Velho RM, O’Malley C, Azevedo LB, Ells LJ, Metzendorf MI, Rees K. Diet, physical activity and behavioural interventions for the treatment of overweight or obese adolescents aged 12 to 17 years. Cochrane Database Syst Rev 2017;6:CD012691.

5. Mühlig Y, Wabitsch M, Moss A, Hebebrand J. Weight loss in children and adolescents. Dtsch Arztebl Int. 2014;28;111(48):818–24. doi: 10.3238/arztebl. 2014.0818.

6. Mead E, Atkinson G, Richter B, Metzendorf MI, Baur L, Finer N, Corpeleijn E, O’Malley C, Ells LJ. Drug interventions for the treatment of obesity in children and adolescents. Cochrane Database Syst Rev 2016;11:CD012436.

7. Cardel MI, Jastreboff AM, Kelly AS. Treatment of Adolescent Obesity in 2020. JAMA 2019;322 (17):1707–1708.

8. Ells LJ, Rees K, Brown T, Mead E, Al-Khudairy L, Azevedo L, McGeechan GJ, Baur L, Loveman E, Clements H, Rayco-Solon P, Farpour-Lambert N, Demaio A. Interventions for treating children and adolescents with overweight and obesity: an overview of Cochrane reviews. Int J Obes (Lond) 2018;42:1823–1833.