title: Effects of exenatide on weight and appetite in overweight adolescents and young adults with Prader-Willi syndrome.
abstract: Prader-Willi syndrome (PWS) is associated with hyperphagia and hyperghrelinemia with major morbidity because of obesity without effective medical treatment targeting hyperphagia. Exenatide (Byetta [synthetic Exendin-4]; AstraZeneca, Wilmington DE) is a GLP-1 receptor agonist which reduces appetite and weight and may be an effective treatment in PWS.
  
  
  
  The objective of this study is to determine the effect of a 6-month trial of exenatide on appetite, weight and gut hormones in youth with PWS.
  
  
  
  Ten overweight and obese subjects with PWS (13-25 years) were recruited for a 6-month open-label, non-randomized, longitudinal study conducted at Children's Hospital Los Angeles. Exenatide was given using standard diabetes dosing without dietary modifications. Weight, body mass index (BMI), truncal fat, appetite and plasma acylated ghrelin were measured over 6 months. Mixed meal tolerance tests were performed at 0 and 6 months.
  
  
  
  Appetite scores significantly decreased from baseline (32.2 ± 8.7) after 1, 3 and 6 moths of treatment (27.5 ± 8.8, 25.4 ± 9.3, and 25.4 ± 7.2 respectively; p = 0.004). Hemoglobin A1c decreased significantly after treatment, but weight, BMI z-score and adiposity did not. There was no significant change in ghrelin.
  
  
  
  This is the first longitudinal investigation of the effects of exenatide in subjects with PWS. It was effective in decreasing appetite, without change in weight or BMI in the short term. Larger, controlled, longer-term trials in patients with PWS are needed to confirm the efficacy and safety of exenatide and to evaluate whether its use might induce weight loss when given in conjunction with behavioural modification.
authors.affiliation: Division of Endocrinology, Seattle Children's Hospital, University of Washington, Seattle, WA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Salehi
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Children's Hospital Los Angeles, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA.
authors.forename: I
authors.initials: I
authors.lastname: Hsu
authors.affiliation: Clinical and Translational Science Institute (CTSI), The Saban Research Institute, Children's Hospital Los Angeles, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA.
authors.forename: C G
authors.initials: CG
authors.lastname: Azen
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Children's Hospital Los Angeles, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA.|The Saban Research Institute, Children's Hospital Los Angeles, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA.
authors.forename: S D
authors.initials: SD
authors.lastname: Mittelman
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Children's Hospital Los Angeles, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA.|The Saban Research Institute, Children's Hospital Los Angeles, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Geffner
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Children's Hospital Los Angeles, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Jeandron
mesh_terms: D000293:Adolescent; D000328:Adult; D001066:Appetite / Q000187:drug effects*; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects*; D000077270:Exenatide; D005260:Female; D054439:Ghrelin / Q000097:blood; D006801:Humans; D006963:Hyperphagia / Q000188:drug therapy / Q000209:etiology*; D054795:Incretins / Q000009:adverse effects / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D009765:Obesity / Q000188:drug therapy / Q000209:etiology*; D010455:Peptides / Q000009:adverse effects / Q000627:therapeutic use*; D011218:Prader-Willi Syndrome / Q000150:complications / Q000188:drug therapy*; D014688:Venoms / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D054439:Ghrelin; D054795:Incretins; D010455:Peptides; D014688:Venoms; D000077270:Exenatide
keywords: Byetta; Prader-Willi syndrome; appetite; exenatide; ghrelin; hyperphagia