Dipeptidyl peptidase-4 inhibitors and pancreatitis risk: a meta-analysis of randomized clinical trials

Diabetes Obes Metab. 2014 Jan;16(1):48-56. doi: 10.1111/dom.12176. Epub 2013 Jul 28.


Aim: Some observational studies reporting an increased risk of pancreatitis in association with Dipeptidyl Peptidase-4 inhibitors (DPP4i) have raised concerns on the overall safety of this class. Aim of the present meta-analysis is the systematic collection of information on pancreatitis in randomized clinical trials with DPP4i.

Data sources: an extensive Medline, Embase and Cochrane Database search for 'vildagliptin', 'sitagliptin', 'saxagliptin', 'alogliptin', 'linagliptin' and 'dutogliptin' was performed up to 1 March 2013.

Study selection: studies were included if they satisfied the following criteria: (i) randomized trials, (ii) duration ≥12 weeks, (iii) on type 2 diabetes and (iv) comparison of DPP4i with placebo or active drugs. The identification and the selection of studies, and the subsequent data extraction were performed independently by two authors. Mantel-Haenszel odds ratio with 95% Confidence Interval (MH-OR) was calculated for all the adverse events defined below. The principal outcome was the effect of DPP4i on the incidence of pancreatitis.

Results: A total of 134 eligible trials were identified. The overall risk of pancreatitis and pancreatic cancer was not different between DPP4i and comparators (MH-OR: 0.93[0.51-1.69]; p = 0.82).

Conclusions: It should be recognized that the number of observed cases of incident pancreatitis is small and the confidence intervals of risk estimates are wide. However, the present meta-analysis do not suggest any increase in the risk of pancreatitis with DPP4i.

Keywords: antidiabetic drug; meta-analysis; type 2 diabetes.

Publication types

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

MeSH terms

  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors / administration & dosage
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects*
  • Drug-Related Side Effects and Adverse Reactions
  • Female
  • Humans
  • Incidence
  • Male
  • Pancreatic Neoplasms / chemically induced*
  • Pancreatitis / chemically induced*
  • Randomized Controlled Trials as Topic
  • Risk Factors


  • Dipeptidyl-Peptidase IV Inhibitors