Efficacy and safety of semaglutide for obesity and hyperphagia in adults with Prader-Willi syndrome
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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 records review 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
Although there was no significant weight loss on semaglutide, 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 adults with PWS, semaglutide produced weight maintenance, reduced 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.
