Endocrine Abstracts

JOINT2275

Prader-Willi syndrome (PWS) is a neurodevelopmental disorder with impaired hypothalamic function due to abnormal DNA methylation within the region of 15q11.2-q13. The available pharmacological options reported for the treatment of hyperphagia and obesity in PWS include Phentermine, Topiramate, Glucagon-like peptide 1 receptor agonist (Exenatide, Liraglutide), Naltrexone- Bupropion and Setmelanotide. However, most of these have been ineffective and some have been withdrawn due to adverse effects. Achieving weight loss in PWS patients is extremely difficult. We report our experience of using a combination therapy of Semaglutide and Methylphenidate in 5 children with PWS to achieve a significant weight loss and improvement in food-seeking behaviors. Five genetically confirmed PWS patients (ages 7, 8, 10, 16, 17 years) were recruited. All had preexisting comorbidities such as T2DM (2), obstructive sleep apnea (5), fatty liver (5). In all 5, other treatment modalities for hyperphagia and obesity like growth hormone, low-calorie diets and laparoscopic sleeve gastrectomy (in one of them) were tried and failed. Hence, they were selected for this combination therapy. The treatment protocol involved using Methylphenidate as an appetite suppressant (starting at 18mg titrated to 36mg, 54mg, 72mg and 108mg) along with Semaglutide (0.5mg titrated to 1mg, 1.5mg and finally 2.4mg). The titrations were made every 3 weeks based on the tolerability. The laboratory parameters, Ghrelin, Leptin, Dykens hyperphagia score, ultrasonography of abdomen, total body composition by DXA, baseline echocardiography was performed for all. This protocol was initiated in 5 children after hospitalization then discharged on combination therapy. Along with therapy they were on low calorie diets. They lost between 6 to 11.5% of weight after 4 to 12 months of starting treatment. In addition, there was complete resolution of T2DM in one of them, improvements in hyperphagia score, sleep apnea and total body composition. It is recommended a moderate weight loss of 5–10% as the goal for medically supervised weight loss. Ghrelin and Leptin were obtained in 2 of them. Ghrelin was 1125pg/ml pre therapy and 1254pg/ml after 1 month in the first. Leptin was 53ng/ml and 36 ng/ml post initiation. The other patient’s Ghrelin was 2627pg/ml pre and 696pg/ml after 7 months. Leptin was 24ng/ml pre and 40ng/ml after 7 months. The anorectic potency of the combination of Semaglutide and Methylphenidate can be utilized in PWS. Significant weight loss can have game-changing effects on complications such as T2DM and severe obstructive sleep apnea. However, this combination therapy warrants further clinical trials.