Publikation

Effects of a single dose of exenatide on appetite, gut hormones, and glucose homeostasis in adults with Prader-Willi syndrome

Wissenschaftlicher Artikel/Review - 01.06.2011

Bereiche
PubMed
DOI

Zitation
Sze L, Campbell L, Steinbeck K, Sainsbury A, Herzog H, Smith E, Loughnan G, Jenkins A, Purtell L, Viardot A. Effects of a single dose of exenatide on appetite, gut hormones, and glucose homeostasis in adults with Prader-Willi syndrome. J Clin Endocrinol Metab 2011; 96:E1314-9.
Art
Wissenschaftlicher Artikel/Review (Englisch)
Zeitschrift
J Clin Endocrinol Metab 2011; 96
Veröffentlichungsdatum
01.06.2011
eISSN (Online)
1945-7197
Seiten
E1314-9
Kurzbeschreibung/Zielsetzung

CONTEXT
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). DESIGN, SETTING, PATIENTS, AND INTERVENTION: 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.

MAIN OUTCOME MEASURES
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.