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

Abstract

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% CI 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.

Keywords: acute pancreatitis; chronic pancreatitis; cohort studies; dipeptidyl peptidase-4 inhibitors; glucagon-like peptide-1 receptor agonists; incretin-based therapy; type 2 diabetes mellitus.