Long-term semaglutide treatment in three Prader-Willi syndrome patients without diabetes showed variable but meaningful results, from preventing weight gain to achieving 14.4% weight loss, with good tolerability.
Up to 14.4% weight lossachieved with semaglutide in a Prader-Willi syndrome patient — a condition where conventional weight management is nearly impossible due to brain-driven insatiable hunger
What the researchers found
Three PWS patients without diabetes received semaglutide (0.5-2 mg weekly) with long-term follow-up. Patient 1: weight maintenance with prevention of further gain. Patient 2: 14.4% weight loss from baseline. Patient 3: 11% weight loss from baseline. One patient had previously undergone metabolic surgery.
Semaglutide was well tolerated across all patients, including post-bariatric surgery. The variable response reflects the complex pathophysiology of PWS obesity, where dysfunction in satiety pathways, reward circuits, and hormonal regulation all contribute.
Why it matters
PWS affects about 1 in 15,000-25,000 births and is the most common genetic cause of severe obesity. Patients have insatiable hunger driven by brain dysfunction that makes conventional weight management nearly impossible. Finding that a GLP-1 drug can help — even in this extreme biological context — suggests semaglutide may work through mechanisms beyond simple appetite suppression.
How the study worked
Case series with long-term follow-up of three PWS patients treated with semaglutide at a single center. Treatment dosages ranged from 0.5 to 2 mg weekly. Clinical outcomes including weight change, tolerability, and safety were monitored. A literature review of GLP-1 RA use in PWS was also conducted.
What this study cannot tell us
This is a case series of only three patients — the smallest possible clinical evidence. There was no control group, and individual responses varied significantly. The optimal dose and duration of semaglutide for PWS are unknown. Long-term effects on the distinctive metabolic and hormonal abnormalities of PWS were not comprehensively assessed. The results cannot be generalized to all PWS patients.
How to read the evidence
This is a case series of three patients, representing the lowest level of clinical evidence. While the results are encouraging, randomized controlled trials are essential to establish efficacy and safety of semaglutide for PWS.
When this study was published
Published in 2024, this case series adds to the small but growing body of evidence on GLP-1 RA use in genetic obesity syndromes.
The bigger picture
GLP-1 drugs are primarily studied in common obesity and diabetes, but their potential in genetic obesity syndromes is largely unexplored. PWS represents perhaps the most challenging obesity phenotype, driven by fundamental brain circuitry dysfunction. If semaglutide can produce meaningful weight loss even in this context, it suggests the drug's central nervous system effects are more powerful than previously appreciated.
Questions still open
- What predicts which PWS patients will respond well to semaglutide versus those who only maintain weight?
- Would higher doses of semaglutide (up to 2.4 mg as used for obesity) produce better results in PWS?
- Could combining semaglutide with other appetite-modifying therapies address PWS's complex obesity pathophysiology?
Common questions
What is Prader-Willi syndrome and why is it so hard to manage weight?
Can semaglutide help with Prader-Willi syndrome obesity?
Read the original research
Case report: Long-term efficacy and safety of semaglutide in the treatment of syndromic obesity in Prader Willi syndrome - case series and literature review.
Frontiers in endocrinology, 15, 1528457
Citation
Koceva, Andrijana; Mlekuš Kozamernik, Katarina; Janež, Andrej; Herman, Rok; Ferjan, Simona; Jensterle, Mojca. (2024). Case report: Long-term efficacy and safety of semaglutide in the treatment of syndromic obesity in Prader Willi syndrome - case series and literature review.. Frontiers in endocrinology, 15, 1528457. https://doi.org/10.3389/fendo.2024.1528457