Glucagon-like peptide-1 receptor agonist exenatide has no acute effect on MRI-measured exocrine pancreatic function in patients with type 2 diabetes: a randomized trial

Diabetes Obes Metab. 2016 Mar;18(3):281-8. doi: 10.1111/dom.12612. Epub 2016 Jan 13.

Abstract

Aims: To investigate the effect of infusion of the glucagon-like peptide-1 (GLP-1) receptor agonist exenatide on exocrine pancreatic function.

Methods: This was a randomized, placebo-controlled, double-blind, crossover study in 12 male patients with type 2 diabetes, treated with oral glucose-lowering agents. On two separate occasions, exenatide or placebo (saline 0.9%) were administered intravenously, in randomized order. Exocrine pancreatic function was measured using secretin-enhanced magnetic resonance cholangiopancreatography. The primary outcome measure was defined as secretin-stimulated pancreatic excretion volume. Secondary outcome measures were maximum secretion speed and the time to reach this maximum. In addition, changes in pancreatic duct (PD) diameter were measured.

Results: Exenatide did not change secretin-stimulated pancreatic excretion volume, as compared with placebo (mean ± standard error of the mean 142.2 ± 15.6 ml vs 142.6 ± 8.5 ml, respectively; p = 0.590). Also, exenatide did not change the maximum secretion speed (33.1 ± 1.4 vs 36.9 ± 2.2; p = 0.221), nor the time to reach this maximum (both 4 min 30 s). No differences in PD diameter were observed between the two groups.

Conclusions: Infusion of exenatide did not directly influence MRI-measured exocrine pancreatic excretion in patients with type 2 diabetes. Although long-term studies are warranted, these findings suggest that potential adverse pancreatic effects of GLP-1 receptor agonists are not mediated by changes in exocrine pancreatic secretion.

Keywords: exenatide; exocrine pancreatic function; glucagon-like peptide-1 receptor agonists; pancreatitis; type 2 diabetes.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cholangiopancreatography, Magnetic Resonance / methods
  • Cross-Over Studies
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Double-Blind Method
  • Exenatide
  • Glucagon-Like Peptide-1 Receptor / agonists*
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Male
  • Middle Aged
  • Pancreas, Exocrine / drug effects*
  • Pancreatic Ducts / pathology
  • Peptides / pharmacology*
  • Secretin / metabolism
  • Venoms / pharmacology*

Substances

  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Peptides
  • Venoms
  • Secretin
  • Exenatide