Efficacy and safety of semaglutide for obesity and hyperphagia in adults with Prader-Willi syndrome
File(s)
Published version
Author(s)
Ahmed, Shahd
Bridges, Nicola
Goldstone, Anthony P
Type
Journal Article
Abstract
Context: Prader-Willi syndrome is a genetic neurodevelopmental disorder characterized by hyperphagia and early-onset obesity from hypothalamic dysfunction with endocrinopathies and learning disability.
Management is challenging with strict control of the food environment needed. While newer glucagon-like
peptide-1 receptor agonists, such as semaglutide, have efficacy in non-PWS obesity, there have been limited
case reports in PWS.
Objective/Design/Setting: Retrospective, observational cohort of 12 adults with PWS and overweight/obesity treated with semaglutide at a UK academic hospital centre specialist clinic.
Patients: Mean ± SD age 28.3 ± 10.1 years, 83% female, BMI 46.6 ± 8.2kg/m², 75% type 2 diabetes mellitus.
Intervention: Median follow-up 17.2 months (range 8.7-36.1) with median semaglutide dose 2.4mg once
weekly (1.0-2.4).
Results: There was no significant overall weight loss on semaglutide, but there was stabilisation of the weight
gain prior to treatment over previous 12.4 months (7.6-23.0): post -3.1 ± 9.9% vs. pre +5.7 ± 5.6%: d -0.72,
P=0.037. There was a significant decrease in hyperphagia on semaglutide from Hyperphagia Questionnaire
for Clinical Trials (n=11, -7.3 ± 6.1 (max 36), d -1.19, P=0.003), having been stable before treatment. HbA1c
improved in those with elevated baseline levels (n=6, -4.2 ± 4.9%, d -0.74, P=0.13). Mild gastrointestinal side
effects were seen in 25% but did not lead to discontinuation.
Conclusions: In this small open-label, observational cohort of adults with PWS, semaglutide produced weight
maintenance though not weight loss, but appeared to reduce hyperphagia, and improved glycaemic control,
with good tolerability. Larger placebo-controlled trials are needed to confirm these findings in adults and
adolescents with PWS, especially in those without T2DM, where efficacy may be greater.
Management is challenging with strict control of the food environment needed. While newer glucagon-like
peptide-1 receptor agonists, such as semaglutide, have efficacy in non-PWS obesity, there have been limited
case reports in PWS.
Objective/Design/Setting: Retrospective, observational cohort of 12 adults with PWS and overweight/obesity treated with semaglutide at a UK academic hospital centre specialist clinic.
Patients: Mean ± SD age 28.3 ± 10.1 years, 83% female, BMI 46.6 ± 8.2kg/m², 75% type 2 diabetes mellitus.
Intervention: Median follow-up 17.2 months (range 8.7-36.1) with median semaglutide dose 2.4mg once
weekly (1.0-2.4).
Results: There was no significant overall weight loss on semaglutide, but there was stabilisation of the weight
gain prior to treatment over previous 12.4 months (7.6-23.0): post -3.1 ± 9.9% vs. pre +5.7 ± 5.6%: d -0.72,
P=0.037. There was a significant decrease in hyperphagia on semaglutide from Hyperphagia Questionnaire
for Clinical Trials (n=11, -7.3 ± 6.1 (max 36), d -1.19, P=0.003), having been stable before treatment. HbA1c
improved in those with elevated baseline levels (n=6, -4.2 ± 4.9%, d -0.74, P=0.13). Mild gastrointestinal side
effects were seen in 25% but did not lead to discontinuation.
Conclusions: In this small open-label, observational cohort of adults with PWS, semaglutide produced weight
maintenance though not weight loss, but appeared to reduce hyperphagia, and improved glycaemic control,
with good tolerability. Larger placebo-controlled trials are needed to confirm these findings in adults and
adolescents with PWS, especially in those without T2DM, where efficacy may be greater.
Date Issued
2026-09-03
Date Acceptance
2026-08-10
Citation
Frontiers in Endocrinology, 2026, 17
ISSN
1664-2392
Publisher
Frontiers Media S.A.
Journal / Book Title
Frontiers in Endocrinology
Volume
17
Copyright Statement
©2026 Ahmed, Bridges and Goldstone. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms
License URL
Publication Status
Published
Article Number
1881392
Date Publish Online
2026-09-03