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Cited by 87Regulation of Appetite and ObesityPharmacology and Obesity TreatmentDiabetes Treatment and Management

A phase 3 randomized clinical trial using a o nce‐weekly glucagon‐like peptide‐1 receptor agonist in adolescents and young adults with hypothalamic obesity

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Roth, Christian L., Perez, Francisco A., Whitlock, Kathryn B., Elfers, Clinton, Yanovski, Jack A., Shoemaker, Ashley H., Abuzzahab, M. Jennifer·2021·Diabetes, Obesity and Metabolism
DOI 10.1111/dom.14224PMC PMC7821019
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Abstract

Aim: To evaluate the efficacy, safety and tolerability of a glucagon‐like peptide‐1 receptor agonist (GLP‐1 RA) in patients with hypothalamic obesity (HO). Materials and Methods: A two‐arm, randomized, multicentre, double‐blind, placebo‐controlled trial was conducted in 10‐ to 25‐year‐olds with hypothalamic injury following intracranial tumour and HO. Participants were randomized to once‐weekly subcutaneous injections of a GLP‐1 RA exenatide 2 mg (ExQW) or placebo for 36 weeks. The primary efficacy endpoint was 36‐week % change in body mass index (BMI). Secondary outcomes included change in body composition (by dual energy x‐ray absorptiometry). Results: Forty‐two participants were randomized to ExQW (n = 23) or placebo (n = 19). Participants were 5 ± 2 years (mean ± SD) postdiagnosis and development of HO (BMI 37.3 ± 7.1 kg/m 2 ). In intention‐to‐treat analysis, the effect of 36‐week ExQW vs. placebo on % Δ BMI was not significant (estimated treatment difference −1.7 ± 1.8%, 95% CI −4.1 to 0.6%, P = .40); however, total body fat mass was reduced (estimated treatment difference −3.1 ± 1.4 kg, 95% CI −5.7 to −0.4 kg, P = .02). There was a significant reduction in waist circumference (estimated effect of treatment −3.5 [95% CI −5.5 to −1.6] cm, P = .004). All patients treated with placebo increased % of adipose tissue, while 50% treated with ExQW had reductions ( P < .001). Mean HbA1c, glucose tolerance and serum lipids did not change significantly with therapy. ExQW was well tolerated. The most frequent adverse events were transient gastrointestinal disturbances (ExQW vs. placebo: nausea 6/23 vs. 3/18, vomiting 4/23 vs. 4/18 and diarrhoea 7/23 vs. 3/18). Conclusions: GLP‐1 RAs are a promising and safe treatment to improve or stabilize HO in children and young adults.

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  • The same previous clinical trial of exenatide in hypothalamic obesity led to a discernible loss of fat mass relative to placebo.

    “one previous clinical trial of exenatide in hypothalamic obesity did not meet its prespecified primary end point of change in BMI, but did lead to a discernible loss of fat mass relative to placebo (41).”

    From Approach to the patient with acquired hypothalamic syndrome (2026) · cites this paper as [41]

  • A previous clinical trial of exenatide in hypothalamic obesity did not meet its prespecified primary end point of change in BMI.

    “one previous clinical trial of exenatide in hypothalamic obesity did not meet its prespecified primary end point of change in BMI, but did lead to a discernible loss of fat mass relative to placebo (41).”

    From Approach to the patient with acquired hypothalamic syndrome (2026) · cites this paper as [41]

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Authors
Roth, C. L., Perez, F. A., Whitlock, K. B., Elfers, C., Yanovski, J. A., Shoemaker, A. H., & Abuzzahab, M. J.
Affiliations
  • University of Washington (US)
  • Seattle Children's Hospital (US)
  • Seattle Children's Research Institute (US)
  • National Institutes of Health (US)
  • Vanderbilt University Medical Center (US)
  • Children’s Minnesota - St. Paul Hospital (US)
Corresponding author
Roth, Christian L.
ORCID
Venue
Diabetes, Obesity and Metabolism
Publisher
Wiley
Published
2020-10-25
Volume
23
Issue
2
Pages
363-373
ISSN
  • 1462-8902 (ISSN-L)
  • 1463-1326
DOI
10.1111/dom.14224
PMC
PMC7821019
OpenAlex
W3091853494
Cited by
87
References
5
Citations by year
2026: 17 · 2025: 15 · 2024: 28 · 2023: 9 · 2022: 13 · 2021: 4 · 2020: 1
FWCI
3.47
Type
journal article
Language
en
Open access
Licence
Locations
  • Diabetes Obesity and Metabolism (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK104936)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords
hypothalamic obesity, GLP-1 receptor agonists, exenatide, weekly dosing, adolescents and young adults, intracranial tumors, body mass index, body composition, fat mass reduction, waist circumference, gastrointestinal adverse effects, obesity treatment
MeSH terms
Glucagon-Like Peptide-1 Receptor, Exenatide, Adolescent, Adult, Child, Diabetes Mellitus, Type 2, Double-Blind Method, Glucagon-Like Peptides, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Obesity, Treatment Outcome, Young Adult

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