A meta-analysis of serious adverse events reported with exenatide and liraglutide: acute pancreatitis and cancer

Diabetes Res Clin Pract. 2012 Nov;98(2):271-84. doi: 10.1016/j.diabres.2012.09.008. Epub 2012 Sep 23.

Abstract

Aims: The association between GLP-1 agonists, acute pancreatitis (AP), any cancer and thyroid cancer is discussed. This meta-analysis was aimed at evaluating the risk of those serious adverse events associated with GLP-1 agonists in patients with type 2 diabetes.

Methods: Medline, EMBASE, Cochrane Library and clinicaltrials.gov were searched in order to identify longitudinal studies evaluating exenatide or liraglutide use and reporting data on AP or cancer. Odds ratios (ORs) were pooled using a random-effects model. I(2) statistics assessed heterogeneity.

Results: Twenty-five studies were included. Neither exenatide (OR 0.84 [95% CI 0.58-1.22], I(2) = 30%) nor liraglutide (OR 0.97 [95% CI 0.21-4.39], I(2) = 0%) were associated with an increased risk of AP, independent of baseline comparator. The pooled OR for cancer associated with exenatide was 0.86 (95% CI 0.29, 2.60, I(2) = 0%) and for liraglutide was 1.35 (95% CI 0.70, 2.59, I(2) = 0%). Liraglutide was not associated with an increased risk for thyroid cancer (OR 1.54 [95% CI 0.40-6.02], I(2) = 0%). For exenatide, no thyroid malignancies were reported.

Conclusions: Current available published evidence is insufficient to support an increased risk of AP or cancer associated with GLP-1 agonists. These rare and long-term adverse events deserve properly monitoring in future studies evaluating GLP-1 agonists.

Publication types

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

MeSH terms

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

Substances

  • Hypoglycemic Agents
  • Peptides
  • Venoms
  • Liraglutide
  • Glucagon-Like Peptide 1
  • Exenatide