title: Effect of exenatide on cholecystokinin-induced gallbladder emptying in fasting healthy subjects.
abstract: Exenatide is a glucagon-like peptide-1 receptor agonist for the treatment of type 2 diabetes and has been shown to lower blood glucose through multiple mechanisms, including glucose-dependent insulin secretion, suppression of postprandial glucagon release and slowing of gastric emptying. The effects of exenatide on biliary motility are unknown. This study evaluated the effect of a single dose of exenatide on cholecystokinin (CCK)-induced gallbladder emptying. Healthy subjects participated in this randomized, 2-period, double-blind crossover study. Fasting subjects received a single subcutaneous injection of exenatide (10 μg) or placebo 60 min before CCK infusion. Gallbladder volume and ejection fraction (EF) were assessed by ultrasonography before, during, and after CCK infusion (0.003 μg/kg infused over 50 min at 2 mL/min). The diameters of the main pancreatic duct and common bile duct were measured sonographically at the same time points before, during, and following CCK infusion. Administration of exenatide did not affect pre-CCK infusion gallbladder volume or EF compared to placebo. During the CCK-infusion, the mean minimum gallbladder volume was similar for exenatide (13.68 mL) and placebo (11.05 mL) (least squares mean [LSM] difference of 2.62 mL; 95% confidence interval [CI], -0.53, 5.78), but the mean maximum EF was lower for exenatide (28.79%) versus placebo (46.13%) (LSM difference of -17.34%; 95% CI, -30.54, -4.13). Exenatide had no clinically significant effects on pancreatic or bile duct diameters. In conclusion, exenatide reduced CCK-induced gallbladder emptying compared with placebo in fasting healthy subjects.
authors.affiliation: Israelitic Hospital, Academic Hospital University of Hamburg, Hamburg, Germany. j.keller@ik-h.de
authors.forename: Jutta
authors.initials: J
authors.lastname: Keller
authors.forename: Michael E
authors.initials: ME
authors.lastname: Trautmann
authors.forename: Harry
authors.initials: H
authors.lastname: Haber
authors.forename: Lai San
authors.initials: LS
authors.lastname: Tham
authors.forename: Tamsin
authors.initials: T
authors.lastname: Hunt
authors.forename: Kenneth
authors.initials: K
authors.lastname: Mace
authors.forename: Helle
authors.initials: H
authors.lastname: Linnebjerg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001652:Bile Ducts / Q000033:anatomy & histology / Q000000981:diagnostic imaging; D001786:Blood Glucose / Q000032:analysis; D002766:Cholecystokinin / Q000008:administration & dosage / Q000494:pharmacology*; D016001:Confidence Intervals; D018592:Cross-Over Studies; D004311:Double-Blind Method; D000077270:Exenatide; D005215:Fasting; D005260:Female; D005704:Gallbladder / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D016473:Gallbladder Emptying / Q000187:drug effects*; D052216:Glucagon-Like Peptide 1 / Q000819:agonists; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D008875:Middle Aged; D009929:Organ Size / Q000187:drug effects; D010183:Pancreatic Ducts / Q000033:anatomy & histology / Q000000981:diagnostic imaging; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D014463:Ultrasonography; D014688:Venoms / Q000008:administration & dosage / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D010455:Peptides; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D002766:Cholecystokinin; D000077270:Exenatide