Anti-diabetic therapies and the risk of acute pancreatitis: a nationwide retrospective cohort study from Taiwan

To examine the relationship between different anti-diabetic therapies (dipeptidyl peptidase-4 (DPP-4), metformin and sulfonylureas) and risk of acute pancreatitis among type 2 diabetic patients in Taiwan, and explore each drug's dose-response relationship.We derived a nationwide retrospective cohort of patients with type 2 diabetes in Taiwan. The inclusion criteria are adult diabetic patients with continuous baseline enrollment, new users of the studied drugs, and without missing demographics. There were 4113/101 498/44 772 DPP-4/Metformin/Sulfonylurea users. Adjusted hazards ratios for pancreatitis associated with DPP-4, derived from Cox proportional hazard models with propensity score weighting, were estimated; dose-response analyses were also conducted.Dipeptidyl peptidase-4 was statistically significantly associated with a decreased risk of acute pancreatitis compared with sulfonylureas (adjusted HR: 0.36, 95%CI [0.17, 0.75]) but not metformin (adjusted HR: 0.67, 95%CI [0.32, 1.41]); metformin was statistically significantly associated with a lower risk of pancreatitis than sulfonylurea (adjusted HR: 0. 53; 95%CI [0.37, 0.76]). In addition, low-dose metformin was statistically significantly associated with a lower risk of pancreatitis compared with high-dose metformin (HR: 0.65; 95%CI [0.44, 0.97]).Our findings suggest that sulfonylureas may potentially be associated with an increased risk of pancreatitis compared with DPP-4 or metformin. Studies with longer follow up, larger sample sizes, and more precise capture of confounders may be needed to determine the risk of pancreatitis associated with incretin based therapies.