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

• Published in: Diabetes, obesity & metabolism obesity & metabolism, 2016-03, Vol.18 (3), p.281-288
• Main Authors: Smits, M. M., Tonneijck, L., Muskiet, M. H. A., Kramer, M. H. H., Diamant, M., Pieters-van den Bos, I. C., van Raalte, D. H., Cahen, D. L.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Agonists; Cholangiopancreatography, Magnetic Resonance - methods; Cross-Over Studies; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - physiopathology; Double-Blind Method; Excretion; exenatide; exocrine pancreatic function; GLP-1 receptor agonists; Glucagon; Glucagon-Like Peptide-1 Receptor - agonists; Humans; Hypoglycemic Agents - pharmacology; Magnetic resonance imaging; Male; Middle Aged; Pancreas; Pancreas, Exocrine - drug effects; Pancreatic Ducts - pathology; pancreatitis; Peptides; Peptides - pharmacology; Placebos; Secretin; Secretin - metabolism; Secretion; type 2 diabetes; Venoms - pharmacology
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/dom.12612

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.