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

• Published in: Pharmacoepidemiology and drug safety Vol. 24; no. 6; pp. 567 - 575
• Main Authors: Chang, Hsien-Yen, Hsieh, Chi-Feng, Singh, Sonal, Tang, Wenze, Chiang, Yi-Ting, Huang, Weng-Foung
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.06.2015; Wiley Subscription Services, Inc
• Subjects: acute pancreatitis; Adolescent; Adult; Aged; anti-diabetic therapies; Cohort Studies; cohort study; Diabetes; Diabetes Mellitus, Type 2 - drug therapy; dipeptidyl peptidase-4; dipeptidyl peptidase‐4, metformin; Dipeptidyl-Peptidase IV Inhibitors - adverse effects; Drug dosages; Drug therapy; Female; Humans; Hypoglycemic Agents - adverse effects; Male; metformin; Metformin - adverse effects; Middle Aged; Pancreas; Pancreatitis - chemically induced; Pancreatitis - epidemiology; pharmacoepidemiology; Pharmacology; Retrospective Studies; Risk Assessment; Risk factors; sulfonylurea; Sulfonylurea Compounds - adverse effects; Taiwan - epidemiology; Young Adult; Taiwan; sulfonylurea; anti-diabetic therapies; cohort study; dipeptidyl peptidase-4, metformin; acute pancreatitis; pharmacoepidemiology
• ISSN: 1053-8569; 1099-1557
• DOI: 10.1002/pds.3770

Aims 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. Materials and Methods 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. Results 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]). Conclusions 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. Copyright © 2015 John Wiley & Sons, Ltd.