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Cited by 25Regulation of Appetite and ObesityPharmacology and Obesity TreatmentPituitary Gland Disorders and Treatments

Treatment of Hypothalamic Obesity With GLP-1 Analogs

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Dimitri, Paul, Roth, Christian L·2024·Journal of the Endocrine Society
DOI 10.1210/jendso/bvae200PMC PMC11655849
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Abstract

Introduction: Congenital and acquired damage to hypothalamic nuclei or neuronal circuits controlling satiety and energy expenditure results in hypothalamic obesity (HO). To date, successful weight loss and satiety has only been achieved in a limited number of affected patients across multiple drug trials. Glucagon-like peptide-1 (GLP-1) acts via central pathways that are independent from the hypothalamus to induce satiety. GLP-1 receptor agonists (GLP-1RAs) may provide an alternative approach to treating HO. Methods: We performed a comprehensive search in Medline, Google Scholar, and clinical trials registries (ClinicalTrials.gov; clinicaltrialsregister.eur). This nonsystematic literature review was conducted to identify scientific papers published from January 2005 to February 2024 using the Pubmed and Embase databases. Key words used were GLP-1, GLP-1RA, hypothalamic obesity, suprasellar tumor, and craniopharyngioma. Results: Our search identified 7 case studies, 5 case series, and 2 published clinical trials relating to the use of GLP-1RAs in HO. All case studies demonstrated weight loss and improved metabolic function. In contrast, results from case series were variable, with some showing no weight loss and others demonstrating moderate to significant weight loss and improved metabolic parameters. In the ECHO clinical trial, nearly half the subjects randomized to weekly exenatide showed reduced body mass index (BMI). Paradoxically, BMI reduction was greater in patients with more extensive hypothalamic injuries. Conclusion: GLP-1RAs potentially offer a new approach to treating HO. There is a need to stratify patients who are more likely to respond. Further randomized controlled trials are required to determine their efficacy either in isolation or combined with other therapies.

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  • In case series of individuals with hypothalamic obesity treated with earlier-generation GLP1RAs, the degree of weight loss was quite variable.

    “The degree of weight loss in case series with earlier-generation GLP1RAs was quite variable (40)”

    From Approach to the patient with acquired hypothalamic syndrome (2026) · cites this paper as [40]

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References 145 · Cited by 25

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Authors
Dimitri, P., & Roth, C. L.
Affiliations
  • Sheffield Children's NHS Foundation Trust (GB)
  • Seattle Children's Hospital (US)
Corresponding author
Roth, Christian L
ORCID
Venue
Journal of the Endocrine Society
Publisher
The Endocrine Society
Published
2024-11-14
Volume
9
Issue
1
Pages
bvae200-bvae200
ISSN
2472-1972 (ISSN-L)
DOI
10.1210/jendso/bvae200
PMC
PMC11655849
OpenAlex
W4404340844
Cited by
25
References
145
Citations by year
2026: 17 · 2025: 8
FWCI
1.39
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of the Endocrine Society (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (submittedVersion)
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 › Pituitary Gland Disorders and Treatments
Keywords
hypothalamic obesity, GLP-1 receptor agonists, glucagon-like peptide-1, exenatide, weight loss, satiety, suprasellar tumor, craniopharyngioma, hypothalamic injury, body mass index, metabolic function

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