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Pediatrics

Energy balance in hypothalamic obesity in response to treatment with a once-weekly GLP-1 receptor agonist

International Journal of Obesity volume 46, pages 623–629 (2022)Cite this article

Subjects

Abstract

Background/Objectives

Hypothalamic obesity (HO) frequently occurs following suprasellar tumors from a combination of decreased energy expenditure and increased energy intake. Glucagon-like peptide-1 receptor agonist (GLP1RA) therapy is associated with increased satiety and energy expenditure. We hypothesized GLP1RA therapy in patients with HO would cause both lower energy intake and increased energy expenditure.

Subjects/Methods

Forty-two patients aged 10-26 years (median 16 years) with HO with suprasellar tumors were randomized to GLP1RA (exenatide extended release once-weekly, ExQW, n = 23) or placebo (n = 19). Thirty seven (81%) patients completed the 36-week double-blind placebo-controlled trial. Total energy expenditure (TEE) was measured with doubly labeled water, physical activity was assessed with actigraphy, and intake was estimated with ad libitum buffet meal. Results are presented as adjusted mean between-group difference.

Results

As compared with treatment with placebo, treatment with ExQW was associated with decreased energy intake during a buffet meal (−1800 kJ (−430 kcal), 95% CI −3 184 to −418 kJ, p = 0.02). There were no significant differences in physical activity between groups. ExQW (vs. placebo) treatment was associated with a decrease in TEE (−695 kJ/day (−166 kcal/day), 95% CI −1 130 to −264 kJ/day, p < 0.01, adjusted for baseline TEE). The treatment effect was still significant after further adjustment for change in body composition (−372 kJ/day (−89 kcal/day), 95% CI −699 to −42 kJ/day, p = 0.04) or change in leptin (−695 kJ/day (−166 kcal/day), 95% CI −1 130 to −264 kJ/day, p < 0.01). This decrease in TEE occurred despite an increase in lean mass and fat mass (1.7 vs. 1.3 kg lean mass, p = 0.88 and 1.5 vs. 4.6 kg fat mass, p = 0.04, ExQW vs. placebo).

Conclusions

Treatment with a GLP1RA was associated with a decrease in food intake but also a decrease in TEE that was disproportionate to change in body composition.

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Author information

Author notes

  1. These authors contributed equally: Christian L. Roth, M. Jennifer Abuzzahab.

Authors and Affiliations

  1. Vanderbilt University Medical Center, Division of Pediatric Endocrinology, Nashville, TN, 37212, USA

    Ashley H. Shoemaker

  2. Vanderbilt University Medical Center, Division of Gastroenterology, Hepatology and Nutrition Nashville, Nashville, TN, 37212, USA

    Heidi J. Silver & Maciej Buchowski

  3. Vanderbilt University Medical Center, Department of Biostatistics, Nashville, TN, 37212, USA

    James C. Slaughter

  4. Section on Growth and Obesity, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 10 Center Drive, Room 1-3330, Bethesda, MD, 20892, USA

    Jack A. Yanovski

  5. Seattle Children’s Research Institute, 1900 Ninth Ave, Seattle, WA, 98101, USA

    Clinton Elfers & Christian L. Roth

  6. Department of Pediatrics, University of Washington, 1959 NE Pacific St, Seattle, WA, 98195, USA

    Christian L. Roth

  7. McNeely Pediatric Diabetes Center and Endocrinology Clinic, Children’s Minnesota, St. Paul, MN, 55102, USA

    M. Jennifer Abuzzahab

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Contributions

CLR, MJA, and AHS performed the study as investigators. HSJ supervised the nutrient analysis. MB analyzed actigraphy and DLW data. AHS and JCS completed the statistical analysis and created figures and tables. CE reviewed the analysis and provided data management. AHS wrote the first manuscript draft. All authors participated in manuscript editing and final approval.

Corresponding author

Correspondence to Ashley H. Shoemaker.

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Competing interests

Astra Zeneca supported the study by providing the active drug and matching placebo. This study was supported by R01DK104936 (CLR, MJA and AHS) from the National Institute of Diabetes and Digestive and Kidney Diseases and CTSA award No. UL1 TR002243 from the National Center for Advancing Translational Sciences. AHS has consulted for Rhythm Pharmaceuticals, Radius Inc., and Saniona A/S on studies of obesity. JAY reports receiving grant support from the Intramural Research Program of NICHD, NIH, as well as grants from Hikma Pharmaceuticals, Soleno Therapeutics, and Rhythm Pharmaceuticals, for studies of obesity.

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Shoemaker, A.H., Silver, H.J., Buchowski, M. et al. Energy balance in hypothalamic obesity in response to treatment with a once-weekly GLP-1 receptor agonist. Int J Obes 46, 623–629 (2022). https://doi.org/10.1038/s41366-021-01043-6

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