Using real-world data to evaluate the association of incretin-based therapies with risk of acute pancreatitis: a meta-analysis of 1,324,515 patients from observational studies

Diabetes Obes Metab. 2015 Jan;17(1):32-41. doi: 10.1111/dom.12386. Epub 2014 Oct 6.


Aim: To investigate the real-world incidence of acute pancreatitis (AP) associated with incretin-based therapy (IBT).

Methods: We carried out a systematic review and meta-analysis of observational studies using Medline, PubMed, Embase, the Cochrane Database, and conference proceedings. We included: those studies in which AP was a pre-defined clinical outcome; longitudinal studies (case-control, cohort); studies that adjusted for confounders; studies that reported on a population exposed to IBT; studies in which non-IBT users or past users (who received IBTs >90 days before the index date) were used as the control group; studies that reported risk estimates [relative risks, odds ratios (ORs) or hazard ratios] with 95% confidence intervals (CIs) for AP event with IBT use, or that reported sufficient data to estimate these; and publications in the English language. Data were extracted by two independent investigators, and a consensus was reached with involvement of a third. Study-specific ORs from seven cohort studies and two case-control studies were meta-analysed using random-effects models. Associations were tested in subgroups representing different patient characteristics and study quality.

Results: A total of nine studies that included 1,324,515 patients and 5195 cases of AP were included in our meta-analysis. The summary estimate of OR for an association between IBT and AP was 1.03 (95% CI 0.87-1.20).

Conclusions: The present meta-analysis of real-world data does not suggest that IBT is associated with AP. Although we should continue to remain vigilant, IBTs should be regarded as reasonable options to consider adding to the regimen of a patient with type 2 diabetes.

Keywords: acute pancreatitis; case-control study; cohort study; dipeptidyl peptidase-4 inhibitors; glucagon-like peptide-1 receptor agonists; incretin-based therapies; meta-analysis; observational study.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
  • Drug Therapy, Combination / adverse effects
  • Glucagon-Like Peptide-1 Receptor
  • Humans
  • Hypoglycemic Agents / adverse effects*
  • Hypoglycemic Agents / therapeutic use
  • Incretins / adverse effects*
  • Incretins / therapeutic use
  • Observational Studies as Topic
  • Pancreatitis / chemically induced*
  • Pancreatitis / epidemiology
  • Receptors, Glucagon / antagonists & inhibitors
  • Risk Factors


  • Dipeptidyl-Peptidase IV Inhibitors
  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Incretins
  • Receptors, Glucagon