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Current and future pharmacotherapies for obesity in children and adolescents

Nature Reviews Endocrinology volume 19, pages 534–541 (2023)Cite this article

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Abstract

Obesity is a common chronic disease in children and adolescents and its prevalence is increasing worldwide. The causes are multifactorial but involve biological predisposition towards a specific body-weight set point and defended adipose tissue mass converging with an obesogenic environment. Comprehensive treatment of paediatric obesity includes lifestyle modification therapy, anti-obesity medications (AOMs) and/or metabolic surgery. Lifestyle modification therapy used alone produces fairly modest weight loss for most youth with obesity. The emergence of new AOMs has changed the landscape of paediatric weight management, improving the outlook for youth with obesity. This Review briefly highlights obesity development pathways in youth and the role that pharmacotherapy can play in counteracting these pathophysiological forces. Here, results from adolescent AOM clinical trials published since 2020 are reviewed, including the safety, efficacy and tolerability of the newest treatments (glucagon-like peptide 1 receptor agonists and phentermine–topiramate). The importance of a comprehensive and chronic care model, including both lifestyle modification and ongoing pharmacotherapy, will be discussed in the context of maximizing long-term health outcomes. Finally, insight will be provided into the emerging pipeline of AOMs (for example, incretin receptor co-agonists and tri-agonists) and how future therapies might fundamentally change the prognosis for youth with obesity.

Key points

  • Obesity tracks strongly from childhood into adulthood and develops from the convergence of biological predisposition and environmental triggers.

  • The body vigorously defends adipose tissue stores, particularly in adolescence, and lifestyle modification often fails as a sole intervention to treat obesity.

  • Anti-obesity medications (AOMs) target the underlying pathophysiology responsible for obesity, including appetite, satiety and reward pathways, enabling individuals to adhere to a healthy lifestyle.

  • Clinical trials in adolescents with obesity evaluating glucagon-like peptide 1 receptor agonists (liraglutide and semaglutide) or phentermine–topiramate show these AOMs to be safe and effective for inducing weight reduction in this population.

  • Numerous AOMs are in the pipeline at various stages of development; the anticipated mean weight reduction induced by some of these AOMs ranges from 20% to 30%.

  • Health-care providers now have a broad spectrum of treatments to offer their paediatric patients with obesity, including highly effective AOMs and metabolic surgery.

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Fig. 1: Weight gain and obesity result from the convergence of biological predisposition and environmental triggers.
Fig. 2: Weight regain after treatment withdrawal in the adult semaglutide trial.

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Authors and Affiliations

  1. Department of Pediatrics and Center for Pediatric Obesity Medicine, University of Minnesota Medical School, Minneapolis, MN, USA

    Aaron S. Kelly

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Correspondence to Aaron S. Kelly.

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Competing interests

A.S.K. engages in unpaid consulting and educational activities for Novo Nordisk, Vivus, Eli Lilly, and Boehringer Ingelheim and receives donated drugs/placebo from Vivus and donated drugs from Novo Nordisk for National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)-funded clinical trials.

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Kelly, A.S. Current and future pharmacotherapies for obesity in children and adolescents. Nat Rev Endocrinol 19, 534–541 (2023). https://doi.org/10.1038/s41574-023-00858-9

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