Acute Pancreatitis in Patients with Type 2 Diabetes Mellitus Treated with Dipeptidyl Peptidase-4 Inhibitors: A Population-Based Nested Case-Control Study

Concern about an increasing risk of acute pancreatitis associated with incretin-based drugs, including dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 analogs, has emerged recently. This nested case-control study examined the association between the use of DPP-4 inhibitors and acute pancreatitis using Taiwan's National Health Insurance Research Database. From a study cohort of patients with type 2 diabetes mellitus, we identified 1,957 acute pancreatitis cases (patients who had been admitted with a diagnosis of acute pancreatitis) and 7,828 age-, sex-, and cohort entry year-matched controls between 2000 and 2011. Multivariate conditional regression models were used to estimate the association between the use of DPP-4 inhibitors and acute pancreatitis. Sensitivity analyses were conducted by varying the definitions of timing of exposure to DPP-4 inhibitors. The risks of acute pancreatitis among current and past users of DPP-4 inhibitors were comparable with those of non-users (current users: adjusted odds ratio (aOR) 1.04; 95 % CI [0.89-1.21]; past users: aOR 1.61 [0.93-2.77]). Similar results were found in sensitivity analyses with various definitions of "current users" of DPP-4 inhibitors. Nevertheless, the adjusted risk of acute pancreatitis was found to be increased significantly in patients with gallstone disease (aOR 5.89 [4.71-7.35]), alcohol-related disease (aOR 5.36 [4.05-7.08]), hypertriglyceridemia (aOR 1.80 [1.26-2.56]), pancreatic disease (aOR 17.29 [10.60-28.19]), and a higher Diabetes Complications Severity Index (DCSI) score (DCSI 3-4: aOR 1.49 [1.21-1.84]; DCSI a parts per thousand yen5: aOR 1.32 [1.01-1.73]). This population-based study extends previous evidence by exploring the potential association between DPP-4 inhibitor use and the risk of acute pancreatitis in an ethnic Chinese type 2 diabetic cohort. We found that underlying diseases and severity of diabetes but not DPP-4 inhibitor use were associated with acute pancreatitis.