Use of incretin agents and risk of acute and chronic pancreatitis: A population-based cohort study

Lotte M. Knapen, Roy G. P. J. de Jong, Johanna H. M. Driessen, Yolande C. Keulemans, Nielka P. van Erp, Marie L. De Bruin, Hubert G. M. Leufkens, Sander Croes, Frank de Vries*

*Corresponding author for this work

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Aim: To determine the association between the use of incretin agents (dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists) for the treatment of type 2 diabetes mellitus (T2DM) and the risk of any, acute and chronic pancreatitis.

Research design and methods: A population-based cohort study was conducted using data from the UK Clinical Practice Research Datalink (CPRD 2007-2012). A total of 182 428 adult patients with >= 1 non-insulin antidiabetic drug (NIAD) prescription were matched to control subjects without diabetes. Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of pancreatitis in incretin-users (N = 28 370) compared with controls and with other NIAD users. Adjustments were made for lifestyle, disease and drug history. In a sensitivity analysis, a new-user design was used.

Results: Current incretin users had a 1.5-fold increased risk of any pancreatitis compared with NIAD users (adjusted HR 1.47, 95% CI 1.06-2.04). In incident current incretin users the risk of any and acute pancreatitis was increased 2.1-and 2.0-fold compared with NIAD users (adjusted HR 2.12, 95% Cl 1.31-3.43 and adjusted HR 1.96, 95% CI 1.13-3.41), whereas there was no increased risk found for chronic pancreatitis.

Conclusions: Incretin use was associated with an increased risk of any pancreatitis. Moreover, risk of any and acute pancreatitis was higher when applying a new-user design. We were not able to detect an association with chronic pancreatitis, but the number in this subgroup was small.

Original languageEnglish
Pages (from-to)401-411
Number of pages11
JournalDiabetes Obesity & Metabolism
Issue number3
Publication statusPublished - Mar 2017


  • acute pancreatitis
  • chronic pancreatitis
  • cohort studies
  • dipeptidyl peptidase-4 inhibitors
  • glucagon-like peptide-1 receptor agonists
  • incretin-based therapy
  • type 2 diabetes mellitus
  • RATS

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