Background: Prader-Willi syndrome (PWS) is the most frequent genetic cause of obesity and is often complicated by glucose metabolism alterations. Conventional therapies prescribed in type 2 diabetes mellitus (T2DM), like oral hypoglycemic agents and insulin, frequently failed to achieve adequate glycemic control in patients with PWS. Beneficial effects of the glucagon like peptide-1 receptor agonists (GLP1RAs) exenatide and liraglutide have been reported for the management of T2DM in PWS, but no data are currently available on the use of semaglutide, belonging to the same class of drugs, in this particular population.
Case presentation: We report for the first time the use of semaglutide 1 mg per week in an adult patient with genetically confirmed PWS complicated by poor controlled diabetes and severe obesity. At baseline his HbA1c was 11.1%, body weight 99.5 kg, BMI 37.5 kg/m2. He was on a multi-injection insulin therapy, with a total daily insulin dose of 180 IU, in addition to metformin 3000 mg/day. After 6 months of semaglutide treatment, his weight had fallen to 93.9 kg (-5.6 kg, BMI 39.1 kg/m2) and HbA1c had dropped to 7.7% (-3.4%). After 12 months, his weight had plateaued at 94.3 kg (-5.2 kg, BMI 39.3 kg/m2) and HbA1c further improved until 7.2% (- 3.9%). As assessed by bioimpedentiometry, there was also a notable decrease in fat mass (-4.9 kg), without significant changes in lean mass, and a progressive reduction in insulin requirements up to 140 IU (-40 IU/day). The patient well tolerated the therapy and no adverse events were reported. Interestingly, our patient had previously tried liraglutide therapy in adjunction to metformin and insulin therapy reporting no substantial efficacy.
Conclusions: The beneficial effects of semaglutide on glycemic control and weight reduction provide a promising treatment for diabetes and obesity in PWS. This treatment could also be successfully used in combination with insulin, to reduce the dosage of the latter and to avoid weight gain frequently related to its use, and could be even considered in those patients who have already tried a treatment period with liraglutide or other GLP1RAs with no substantial efficacy. Further studies are required to confirm the efficacy and safety of semaglutide in patients with PWS.
21 May 2022 - 24 May 2022