ESPE Yearbook of Paediatric Endocrinology

Ashley.H.Shoemaker@VUMC.org International Journal of Obesity 2022, Epub 2022 Jan 3. doi: 10.1038/s41366-021-01043-6. https://pubmed.ncbi.nlm.nih.gov/34975146/

Brief Summary: This double-blind, placebo-controlled trial assessed the efficacy of 36 weeks of GLP1RA treatment with exenatide extended release once-weekly on weight loss and energy balance in 42 patients (aged 10–26) with hypothalamic obesity (HO) caused by suprasellar tumors. The results showed a decrease in food intake but also a decrease in total energy expenditure.

Glucagon-like peptide-1 receptor agonists (GLP1RA) are known to cause weight loss in adults [1] and adolescents [2] with obesity through mechanism independent of intact hypothalamic structures. In a previous study of GLP1RA, patients with HO did not achieve weight loss but showed a slower increase in BMI and body fat than placebo controls [3]. In this second analysis in patients with HO, the authors show that GLP1RA compared to placebo reduced energy intake during a buffet meal (−1800 kJ, 95% CI – 3184 to −418 kJ, P=0.02) but also reduced total energy expenditure (−327 kJ/day, 95% CI −699 to −42kJ/day, P=0.04) measured using doubly labeled water. In contrast to the continuous increase in BMI in patients with HO treated with GLP1RA, the results of energy intake and total energy expenditure are in line with the results of previous studies in patients with obesity treated with GLP1RA [4–6]. The authors could not explain the unexpected reduction in total energy expenditure without weight loss in patients with HO, despite they controlled for physical activity, which remained unchanged during treatment.

This is a well-designed study that investigated the effects of GLP1RA in patients with HO on energy balance using the entire spectrum of currently available methods to assess energy intake, free-living energy expenditure, hyperphagia, and hunger and satiety sensations. Future studies are needed to explain the observed reduction in total energy expenditure without observing weight loss during GLP1RA treatment in patients with HO. This research will help to understand the underlying biological mechanisms of energy balance and hunger and satiety regulation in patients with HO.

References: 1. Lomenick, JP, Buchowski MS, Shoemaker AH. A 52-week pilot study of the effects of exenatide on body weight in patients with hypothalamic obesity. Obesity (Silver Spring), 2016. 24(6): p. 1222–5. 2. Kelly AS, et al. A Randomized, Controlled Trial of Liraglutide for Adolescents with Obesity. N Engl J Med, 2020. 382(22): p. 2117–2128. 3. Roth CL, et al. A phase 3 randomized clinical trial using a once-weekly glucagon-like peptide-1 receptor agonist in adolescents and young adults with hypothalamic obesity. Diabetes Obes Metab, 2021. 23(2): p. 363–373. 4. van Can, J et al. Effects of the once-daily GLP-1 analog liraglutide on gastric emptying, glycemic parameters, appetite and energy metabolism in obese, non-diabetic adults. Int J Obes (Lond), 2014. 38(6): p. 784–93. 5. Blundell J., et al. Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity. Diabetes Obes Metab, 2017. 19(9): p. 1242–1251. 6. Horowitz M., et al. Effect of the once-daily human GLP-1 analogue liraglutide on appetite, energy intake, energy expenditure and gastric emptying in type 2 diabetes. Diabetes Res Clin Pract, 2012. 97(2): p. 258–66.