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
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Obesity tracks strongly from childhood into adulthood and develops from the convergence of biological predisposition and environmental triggers.
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The body vigorously defends adipose tissue stores, particularly in adolescence, and lifestyle modification often fails as a sole intervention to treat obesity.
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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.
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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.
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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%.
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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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References
Hales, C. M., Fryar, C. D., Carroll, M. D., Freedman, D. S. & Ogden, C. L. Trends in obesity and severe obesity prevalence in US youth and adults by sex and age, 2007–2008 to 2015–2016. J. Am. Med. Assoc. 319, 1723–1725 (2018).
Woolford, S. J. et al. Changes in body mass index among children and adolescents during the COVID-19 pandemic. J. Am. Med. Assoc. 326, 1434–1436 (2021).
World Obesity Federation. World Obesity Federation Childhood Obesity Atlas Report in 2019 https://www.worldobesity.org/membersarea/global-atlas-on-childhood-obesity (2019).
Freedman, D. S., Mei, Z., Srinivasan, S. R., Berenson, G. S. & Dietz, W. H. Cardiovascular risk factors and excess adiposity among overweight children and adolescents: the Bogalusa Heart Study. J. Pediatr. 150, 12–17 (2007).
Jastreboff, A. M., Kotz, C. M., Kahan, S., Kelly, A. S. & Heymsfield, S. B. Obesity as a disease: the Obesity Society 2018 position statement. Obesity 27, 7–9 (2019).
Kumar, S. & Kelly, A. S. Review of childhood obesity: from epidemiology, etiology, and comorbidities to clinical assessment and treatment. Mayo Clin. Proc. 92, 251–265 (2017).
Jebeile, H., Kelly, A. S., O’Malley, G. & Baur, L. A. Obesity in children and adolescents: epidemiology, causes, assessment, and management. Lancet Diabetes Endocrinol. 10, 351–365 (2022).
Twig, G. et al. BMI at age 17 years and diabetes mortality in midlife: a nationwide cohort of 2.3 million adolescents. Diabetes Care 39, 1996–2003 (2016).
Twig, G. et al. Body-mass index in 2.3 million adolescents and cardiovascular death in adulthood. N. Engl. J. Med. 374, 2430–2440 (2016).
Bouchard, C. Genetics of obesity: what we have learned over decades of research. Obesity 29, 802–820 (2021).
Hinney, A., Korner, A. & Fischer-Posovszky, P. The promise of new anti-obesity therapies arising from knowledge of genetic obesity traits. Nat. Rev. Endocrinol. 18, 623–637 (2022).
Leibel, R. L., Rosenbaum, M. & Hirsch, J. Changes in energy expenditure resulting from altered body weight. N. Engl. J. Med. 332, 621–628 (1995).
MacLean, P. S., Bergouignan, A., Cornier, M. A. & Jackman, M. R. Biology’s response to dieting: the impetus for weight regain. Am. J. Physiol. Regul. Integr. Comp. Physiol. 301, R581–R600 (2011).
Sumithran, P. et al. Long-term persistence of hormonal adaptations to weight loss. N. Engl. J. Med. 365, 1597–1604 (2011).
Hayes, J. F., Eichen, D. M., Barch, D. M. & Wilfley, D. E. Executive function in childhood obesity: promising intervention strategies to optimize treatment outcomes. Appetite 124, 10–23 (2018).
Nederkoorn, C., Braet, C., Van Eijs, Y., Tanghe, A. & Jansen, A. Why obese children cannot resist food: the role of impulsivity. Eat. Behav. 7, 315–322 (2006).
Kulendran, M. et al. Neuropsychological assessment as a predictor of weight loss in obese adolescents. Int. J. Obes. 38, 507–512 (2014).
Pearce, A. L., Leonhardt, C. A. & Vaidya, C. J. Executive and reward-related function in pediatric obesity: a meta-analysis. Child Obes. 14, 265–279 (2018).
Ells, L. J. et al. Interventions for treating children and adolescents with overweight and obesity: an overview of Cochrane reviews. Int. J. Obes. 42, 1823–1833 (2018).
O’Connor, E. A. et al. Screening for obesity and intervention for weight management in children and adolescents: evidence report and systematic review for the US preventive services task force. J. Am. Med. Assoc. 317, 2427–2444 (2017).
Larsen, P. J., Fledelius, C., Knudsen, L. B. & Tang-Christensen, M. Systemic administration of the long-acting GLP-1 derivative NN2211 induces lasting and reversible weight loss in both normal and obese rats. Diabetes 50, 2530–2539 (2001).
Drucker, D. J. GLP-1 physiology informs the pharmacotherapy of obesity. Mol. Metab. 57, 101351 (2022).
van Bloemendaal, L., Ten Kulve, J. S., la Fleur, S. E., Ijzerman, R. G. & Diamant, M. Effects of glucagon-like peptide 1 on appetite and body weight: focus on the CNS. J. Endocrinol. 221, T1–T16 (2014).
Pi-Sunyer, X. et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. N. Engl. J. Med. 373, 11–22 (2015).
Wadden, T. A. et al. Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: the SCALE maintenance randomized study. Int. J. Obes. 37, 1443–1451 (2013).
Kelly, A. S. et al. A randomized, controlled trial of liraglutide for adolescents with obesity. N. Engl. J. Med. 382, 2117–2128 (2020). This paper reports on the results of the large phase III trial of liraglutide in adolescents with obesity that served as the basis for regulatory approval.
Food and Drug Administration. FDA Approves Weight Management Drug for Patients Aged 12 and Older https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-weight-management-drug-patients-aged-12-and-older (2020).
MedwireNews. EMA Approves Liraglutide for Teenagers with Obesity https://diabetes.medicinematters.com/en-GB/liraglutide–obesity-/adolescents/ema-approves-liraglutide-for-teenagers-with-obesity/19028106 (2021).
Wilding, J. P. H. et al. Once-weekly semaglutide in adults with overweight or obesity. N. Engl. J. Med. 384, 989–1002 (2021).
Wadden, T. A. et al. Effect of subcutaneous semaglutide vs placebo as an adjunct to intensive behavioral therapy on body weight in adults with overweight or obesity: the STEP 3 randomized clinical trial. J. Am. Med. Assoc. 325, 1403–1413 (2021).
Rubino, D. et al. Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: the STEP 4 randomized clinical trial. J. Am. Med. Assoc. 325, 1414–1425 (2021).
Rubino, D. M. et al. Effect of weekly subcutaneous semaglutide vs daily liraglutide on body weight in adults with overweight or obesity without diabetes: the STEP 8 randomized clinical trial. J. Am. Med. Assoc. 327, 138–150 (2022).
Weghuber, D. et al. Once-weekly semaglutide in adolescents with obesity. N. Engl. J. Med. 387, 2245–2257 (2022). This paper reports on the results of the large phase III trial of semaglutide in adolescents with obesity that served as the basis for regulatory approval.
MedwireNews. FDA Approves High-dose Semaglutide for Adolescents with Obesity https://diabetes.medicinematters.com/en-GB/semaglutide/obesity/us-fda-children-obesity/23902216 (2023).
European Medicines Agency. Union Register of Medicinal Products for Human Use https://ec.europa.eu/health/documents/community-register/html/h1608.htm (2023).
Gadde, K. M. et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet 377, 1341–1352 (2011).
Garvey, W. T. et al. Two-year sustained weight loss and metabolic benefits with controlled-release phentermine/topiramate in obese and overweight adults (SEQUEL): a randomized, placebo-controlled, phase 3 extension study. Am. J. Clin. Nutr. 95, 297–308 (2012).
Allison, D. B. et al. Controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP). Obesity 20, 330–342 (2012).
Kelly, A. S. et al. Phentermine/topiramate for the treatment of adolescent obesity. NEJM Evid. https://doi.org/10.1056/evidoa2200014 (2022). This paper reports on the results of the large phase III trial of phentermine–topiramate in adolescents with obesity that served as the basis for regulatory approval.
Food and Drug Administration. FDA Approves Treatment for Chronic Weight Management in Pediatric Patients Aged 12 Years and Older https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-treatment-chronic-weight-management-pediatric-patients-aged-12-years-and-older (2022).
Kelly, A. S. et al. Severe obesity in children and adolescents: identification, associated health risks, and treatment approaches: a scientific statement from the American Heart Association. Circulation 128, 1689–1712 (2013).
Ryder, J. R., Fox, C. K. & Kelly, A. S. Treatment options for severe obesity in the pediatric population: current limitations and future opportunities. Obesity 26, 951–960 (2018).
Hampl, S. E. et al. Clinical practice guideline for the evaluation and treatment of children and adolescents with obesity. Pediatrics 151, e2022060640 (2023).
Aldawsari, M. et al. The efficacy of GLP-1 analogues on appetite parameters, gastric emptying, food preference and taste among adults with obesity: systematic review of randomized controlled trials. Diabetes Metab. Syndr. Obes. 16, 575–595 (2023).
Rubino, F. et al. Joint international consensus statement for ending stigma of obesity. Nat. Med. 26, 485–497 (2020).
Puhl, R. M. & Lessard, L. M. Weight stigma in youth: prevalence, consequences, and considerations for clinical practice. Curr. Obes. Rep. 9, 402–411 (2020).
Wilding, J. P. H. et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension. Diabetes Obes. Metab. 24, 1553–1564 (2022).
Del Prato, S., Gallwitz, B., Holst, J. J. & Meier, J. J. The incretin/glucagon system as a target for pharmacotherapy of obesity. Obes. Rev. 23, e13372 (2022).
Hammoud, R. & Drucker, D. J. Beyond the pancreas: contrasting cardiometabolic actions of GIP and GLP1. Nat. Rev. Endocrinol. 19, 201–216 (2022).
Jastreboff, A. M. et al. Tirzepatide once weekly for the treatment of obesity. N. Engl. J. Med. 387, 205–216 (2022).
Mathiesen, D. S., Bagger, J. I. & Knop, F. K. Long-acting amylin analogues for the management of obesity. Curr. Opin. Endocrinol. Diabetes Obes. 29, 183–190 (2022).
Lau, D. C. W. et al. Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial. Lancet 398, 2160–2172 (2021).
Enebo, L. B. et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2.4 mg for weight management: a randomised, controlled, phase 1b trial. Lancet 397, 1736–1748 (2021).
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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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DOI: https://doi.org/10.1038/s41574-023-00858-9
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