Glucagon-like peptide-1 receptor agonists and pancreatitis: a meta-analysis of randomized clinical trials

Diabetes Res Clin Pract. 2014 Feb;103(2):269-75. doi: 10.1016/j.diabres.2014.01.010. Epub 2014 Jan 14.

Abstract

Aims: Several randomized trials with metabolic outcomes have reported that glucagon like peptide-1 receptor agonists (GLP-1 RA) could be associated with an increased risk of pancreatitis. The present meta-analysis aimed to examine this hypothesis.

Methods: An extensive Medline, Embase, and Cochrane Database search for "exenatide", "liraglutide", "albiglutide", "taspoglutide", "dulaglutide", "lixisenatide", and "semaglutide" was performed up to March 31st, 2013.

Inclusion criteria: (i) randomized trials, (ii) duration ≥12 weeks; (iii) on type 2 diabetes; and (iv) comparison of GLP-1RA with placebo or active drugs. Mantel-Haenszel odds ratio with 95% confidence interval (MH-OR) was calculated for pancreatitis.

Results: 80 eligible trials were identified. Of these, 39 had not disclosed their findings or did not report any information on pancreatitis. The remaining 41 trials enrolled 14,972 patients, with a total exposure of 14,333 patient × years (8353 and 5980 patient × years for GLP-1 receptor agonists and comparators, respectively). The overall risk of pancreatitis was not different between GLP-1RA and comparators (MH-OR: 1.01[0.37; 2.76]; p = 0.99).

Conclusions: The present meta-analysis does not suggest any increase in the risk of pancreatitis with the use of GLP-1RA. However, it should be recognized that the number of observed cases of incident pancreatitis is very small and the confidence intervals of risk estimates are wide.

Keywords: Glucagon like peptide-1 receptor agonists; Meta-analysis; Pancreatitis.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Diabetes Mellitus, Type 2 / drug therapy*
  • Exenatide
  • Glucagon-Like Peptide 1 / adverse effects
  • Glucagon-Like Peptide 1 / analogs & derivatives
  • Glucagon-Like Peptide 1 / therapeutic use
  • Glucagon-Like Peptide-1 Receptor
  • Humans
  • Hypoglycemic Agents / adverse effects*
  • Hypoglycemic Agents / therapeutic use
  • Liraglutide
  • Pancreatitis / chemically induced*
  • Peptides / adverse effects
  • Peptides / therapeutic use
  • Randomized Controlled Trials as Topic
  • Receptors, Glucagon / agonists*
  • Venoms / adverse effects
  • Venoms / therapeutic use

Substances

  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Peptides
  • Receptors, Glucagon
  • Venoms
  • taspoglutide
  • rGLP-1 protein
  • lixisenatide
  • Liraglutide
  • Glucagon-Like Peptide 1
  • Exenatide