title: Effects of a single dose of exenatide on appetite, gut hormones, and glucose homeostasis in adults with Prader-Willi syndrome.
abstract: BACKGROUND
  Prader-Willi syndrome (PWS) is associated with hyperphagia and obesity, without effective pharmacological treatment. Exenatide, recently developed for treatment of type 2 diabetes, induces appetite suppression and weight loss with common side effects.
  
  
  OBJECTIVE
  The objective of the study was to investigate the initial safety and effectiveness of exenatide in adult PWS subjects compared with obese controls (OBESE).
  
  
  METHODS
  Eight PWS and 11 OBESE patients underwent standardized meal studies after a single sc injection of 10 μg exenatide or placebo in a single-blinded, crossover design.
  
  
  METHODS
  Glucose, insulin, C-peptide, glucagon, peptide YY (PYY; total)/PYY (3-36), glucagon-like peptide-1, and ghrelin (total) were measured fasting and postprandially. Appetite and satiety were assessed by visual analog scales. Energy expenditure (EE) was measured by indirect calorimetry. Side effects were screened during and for 24 h after the meal.
  
  
  RESULTS
  PWS and OBESE patients were matched for gender, age, body mass index, and central/total body fat. In both groups, exenatide increased satiety and lowered glucose and insulin levels but increased insulin secretion rate. Side effects were absent in PWS but common in OBESE patients. During the meal, PYY (total) and ghrelin were elevated in PWS patients. Exenatide decreased PYY (total) and glucagon-like peptide-1, whereas ghrelin remained unchanged. Energy expenditure was unchanged by exenatide.
  
  
  CONCLUSIONS
  Our pilot study demonstrates that exenatide is well tolerated in PWS patients. It increases satiety independently of measured appetite hormones, exerting glucose lowering, and insulinotropic effects similarly in PWS and OBESE patients. Larger prospective studies should investigate whether chronic exenatide administration will reduce hyperphagia and overweight in PWS patients without side effects.
authors.affiliation: Diabetes and Obesity Research Program, Garvan Institute of Medical Research, Sydney-Darlinghurst, New South Wales 2010, Australia.
authors.forename: Lisa
authors.initials: L
authors.lastname: Sze
authors.forename: Louise
authors.initials: L
authors.lastname: Purtell
authors.forename: Arthur
authors.initials: A
authors.lastname: Jenkins
authors.forename: Georgina
authors.initials: G
authors.lastname: Loughnan
authors.forename: Ellie
authors.initials: E
authors.lastname: Smith
authors.forename: Herbert
authors.initials: H
authors.lastname: Herzog
authors.forename: Amanda
authors.initials: A
authors.lastname: Sainsbury
authors.forename: Katharine
authors.initials: K
authors.lastname: Steinbeck
authors.forename: Lesley V
authors.initials: LV
authors.lastname: Campbell
authors.forename: Alexander
authors.initials: A
authors.lastname: Viardot
mesh_terms: D000328:Adult; D001066:Appetite / Q000187:drug effects*; D001786:Blood Glucose / Q000378:metabolism*; D018592:Cross-Over Studies; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D000077270:Exenatide; D005260:Female; D005768:Gastrointestinal Hormones / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D006815:Hunger / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism; D010455:Peptides / Q000008:administration & dosage* / Q000009:adverse effects; D010865:Pilot Projects; D010919:Placebos; D011218:Prader-Willi Syndrome / Q000188:drug therapy* / Q000378:metabolism; D012528:Satiety Response / Q000187:drug effects; D014280:Triglycerides / Q000097:blood; D014688:Venoms / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D001786:Blood Glucose; D005768:Gastrointestinal Hormones; D007004:Hypoglycemic Agents; D010455:Peptides; D010919:Placebos; D014280:Triglycerides; D014688:Venoms; D000077270:Exenatide