Research Article: Efficacy and safety of semaglutide for obesity and hyperphagia in adults with Prader-Willi syndrome
Abstract:
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.
Retrospective, observational cohort of 12 adults with PWS and overweight/obesity treated with semaglutide at a UK academic hospital centre specialist clinic.
Mean ± SD age 28.3 ± 10.1 years, 83% female, BMI 46.6 ± 8.2kg/m², 75% type 2 diabetes mellitus.
Median follow-up 17.2 months (range 8.7-36.1) with median semaglutide dose 2.4mg once weekly (1.0-2.4).
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.
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.
Introduction:
Prader Willi syndrome (PWS) is a rare orphan disease and complex genetic neurodevelopmental disorder, with no licensed treatment for the primary unmet need of controlling hyperphagia and obesity. Nutritional and growth phases in children and adolescents with PWS are well described, with weight gain and hyperphagia leading to obesity later on in childhood if access to food is uncontrolled, with premature mortality primarily due to obesity/diabetes-related complications in adulthood, including cardiorespiratory…
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