title: Anti-diabetic therapies and the risk of acute pancreatitis: a nationwide retrospective cohort study from Taiwan.
abstract: OBJECTIVE
  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.
  
  
  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.
authors: Department of Health Policy & Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.|Center for Drug Safety and Effectiveness, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors: Hsien-Yen
authors: HY
authors: Chang
authors: Institute of Health and Welfare Policy, National Yang-Ming University, Taipei, Taiwan.
authors: Chi-Feng
authors: CF
authors: Hsieh
authors: Center for Drug Safety and Effectiveness, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.|Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.|Division of General Internal Medicine, Johns Hopkins Medicine, Baltimore, MD, USA.
authors: Sonal
authors: S
authors: Singh
authors: Department of Epidemiology and Biostatistics, Milken Institute School of Public Health, The George Washington University, Washington, DC, USA.
authors: Wenze
authors: W
authors: Tang
authors: Institute of Health and Welfare Policy, National Yang-Ming University, Taipei, Taiwan.
authors: Yi-Ting
authors: YT
authors: Chiang
authors: Institute of Health and Welfare Policy, National Yang-Ming University, Taipei, Taiwan.
authors: Weng-Foung
authors: WF
authors: Huang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D008297:Male; D008687:Metformin / Q000009:adverse effects; D008875:Middle Aged; D010195:Pancreatitis / Q000139:chemically induced / Q000453:epidemiology*; D012189:Retrospective Studies; D018570:Risk Assessment; D013453:Sulfonylurea Compounds / Q000009:adverse effects; D013624:Taiwan / Q000453:epidemiology; D055815:Young Adult
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D008687:Metformin
keywords: acute pancreatitis; anti-diabetic therapies; cohort study; dipeptidyl peptidase-4, metformin; pharmacoepidemiology; sulfonylurea