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

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Abstract

Background

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.

Objective

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.

Methods

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.

Results

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 ≥5: aOR 1.32 [1.01–1.73]).

Conclusions

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.

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References

  1. Scheen A. Gliptins (dipeptidyl peptidase-4 inhibitors) and risk of acute pancreatitis. Expert Opin Drug Saf. 2013;12:545–57.

    Article  CAS  PubMed  Google Scholar 

  2. Engel SS, Williams-Herman DE, Golm GT, et al. Sitagliptin: review of preclinical and clinical data regarding incidence of pancreatitis. Int J Clin Pract. 2010;64:984–90.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Cohen D. Reports of pancreatitis are 20-30 times more likely with GLP-1 drugs, analysis finds. BMJ. 2013;346:f2607.

    Article  PubMed  Google Scholar 

  4. Sue M, Yoshihara A, Kuboki K, Hiroi N, Yoshino G. A case of severe acute necrotizing pancreatitis after administration of sitagliptin. Clin Med Insights Case Rep. 2013;6:23–7.

    Article  PubMed Central  PubMed  Google Scholar 

  5. Garg R, Hussey C, Ibrahim S. Pancreatitis associated with the use of sitagliptin and orlistat combination: a case report. Diabet Med. 2010;27:485–6.

    Article  CAS  PubMed  Google Scholar 

  6. US Food and Drug Administration. Sitagliptin (marketed as Januvia and Janumet): reports of acute pancreatitis. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm183800.htm. Accessed 16 May 2013.

  7. US Food and Drug Administration. Information of healthcare professionals: exenatide (marketed as Byetta) - 8/2008 update. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm124713.htm. Accessed 16 May 2013.

  8. Dore DD, Seeger JD, Arnold Chan K. Use of a claims-based active drug safety surveillance system to assess the risk of acute pancreatitis with exenatide or sitagliptin compared to metformin or glyburide. Curr Med Res Opin. 2009;25:1019–27.

    Article  CAS  PubMed  Google Scholar 

  9. Garg R, Chen W, Pendergrass M. Acute pancreatitis in type 2 diabetes treated with exenatide or sitagliptin: a retrospective observational pharmacy claims analysis. Diabetes Care. 2010;33:2349–54.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Williams-Herman D, Round E, Swern AS, et al. Safety and tolerability of sitagliptin in patients with type 2 diabetes: a pooled analysis. BMC Endocr Disord. 2008;8:14.

    Article  PubMed Central  PubMed  Google Scholar 

  11. Gier B, Matveyenko AV, Kirakossian D, Dawson D, Dry SM, Butler PC. Chronic GLP-1 receptor activation by exendin-4 induces expansion of pancreatic duct glands in rats and accelerates formation of dysplastic lesions and chronic pancreatitis in the Kras(G12D) mouse model. Diabetes. 2012;61:1250–62.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Singh S, Chang HY, Richards TM, Weiner JP, Clark JM, Segal JB. Glucagonlike peptide 1-based therapies and risk of hospitalization for acute pancreatitis in type 2 diabetes mellitus: a population-based matched case-control study. JAMA Intern Med. 2013;173:534–9.

    Article  CAS  PubMed  Google Scholar 

  13. Girman CJ, Kou TD, Cai B, et al. Patients with type 2 diabetes mellitus have higher risk for acute pancreatitis compared with those without diabetes. Diabetes Obes Metab. 2010;12:766–71.

    Article  CAS  PubMed  Google Scholar 

  14. Gonzalez-Perez A, Schlienger RG, Rodriguez LA. Acute pancreatitis in association with type 2 diabetes and antidiabetic drugs: a population-based cohort study. Diabetes Care. 2010;33:2580–5.

    Article  PubMed Central  PubMed  Google Scholar 

  15. Noel RA, Braun DK, Patterson RE, Bloomgren GL. Increased risk of acute pancreatitis and biliary disease observed in patients with type 2 diabetes: a retrospective cohort study. Diabetes Care. 2009;32:834–8.

    Article  PubMed Central  PubMed  Google Scholar 

  16. Lai SW, Muo CH, Liao KF, Sung FC, Chen PC. Risk of acute pancreatitis in type 2 diabetes and risk reduction on anti-diabetic drugs: a population-based cohort study in Taiwan. Am J Gastroenterol. 2011;106:1697–704.

    Article  PubMed  Google Scholar 

  17. Shen HN, Chang YH, Chen HF, Lu CL, Li CY. Increased risk of severe acute pancreatitis in patients with diabetes. Diabet Med. 2012;29:1419–24.

    Article  PubMed  Google Scholar 

  18. Shen HN, Lu CL. Incidence, resource use, and outcome of acute pancreatitis with/without intensive care: a nationwide population-based study in Taiwan. Pancreas. 2011;40:10–5.

    Article  CAS  PubMed  Google Scholar 

  19. Hsiao FY, Yang CL, Huang YT, Huang WF. Using Taiwan’s national health insurance research databases for pharmacoepidemiology research. J Food Drug Anal. 2007;15:99–108.

    Google Scholar 

  20. Hsiao FY, Hsieh PH, Huang WF, Tsai YW, Gau CS. Risk of bladder cancer in diabetic patients treated with rosiglitazone or pioglitazone: a nested case-control study. Drug Saf. 2013;36:643–9.

    Article  CAS  PubMed  Google Scholar 

  21. Wen YW, Tsai YW, Huang WF, Hsiao FY, Chen PF. The potentially inappropriate prescription of new drug: thiazolidinediones for patients with type II diabetes in Taiwan. Pharmacoepidemiol Drug Saf. 2011;20:20–9.

    Article  PubMed  Google Scholar 

  22. Hsiao FY, Tsai YW, Wen YW, et al. Relationship between cumulative dose of thiazolidinediones and clinical outcomes in type 2 diabetic patients with history of heart failure: a population-based cohort study in Taiwan. Pharmacoepidemiol Drug Saf. 2010;19:786–91.

    Article  CAS  PubMed  Google Scholar 

  23. Hsiao FY, Mullins CD. The association between thiazolidinediones and hospitalisation for fracture in type 2 diabetic patients: a Taiwanese population-based nested case–control study. Diabetologia. 2010;53:489–96.

    Article  CAS  PubMed  Google Scholar 

  24. Hsiao FY, Huang WF, Wen YW, Chen PF, Kuo KN, Tsai YW. Thiazolidinediones and cardiovascular events in patients with type 2 diabetes mellitus: a retrospective cohort study of over 473,000 patients using the National Health Insurance database in Taiwan. Drug Saf. 2009;32:675–90.

    Article  CAS  PubMed  Google Scholar 

  25. National Health Insurance Research Database [Internet]. Available from http://w3.nhri.org.tw/nhird//en/index.htm. Accessed 20 Sep 2011.

  26. International Classification of Diseases, Ninth Revision (ICD-9). World Health Organization 2011.

  27. Moores K, Gilchrist B, Carnahan R, Abrams T. A systematic review of validated methods for identifying pancreatitis using administrative data. Pharmacoepidemiol Drug Saf. 2012;21(Suppl 1):194–202.

    Article  PubMed  Google Scholar 

  28. Chang HY, Weiner JP, Richards TM, Bleich SN, Segal JB. Validating the adapted Diabetes Complications Severity Index in claims data. Am J Manag Care. 2012;18:721–6.

    PubMed  Google Scholar 

  29. Chang HY, Weiner JP, Richards TM, Bleich SN, Segal JB. Predicting costs with diabetes complications severity index in claims data. Am J Manag Care. 2012;18:213–9.

    PubMed  Google Scholar 

  30. Young BA, Lin E, Von Korff M, et al. Diabetes complications severity index and risk of mortality, hospitalization, and healthcare utilization. Am J Manag Care. 2008;14:15–23.

    PubMed Central  PubMed  Google Scholar 

  31. Hamajima N, Hirose K, Inoue M, Takezaki T, Kuroishi T, Tajima K. Case-control studies: matched controls or all available controls? J Clin Epidemiol. 1994;47:971–5.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by a research grant from the Food and Drug Administration, Taiwan (DOH102-FDA-41100). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Author contributions

Dr. F.-Y. Hsiao and Ms. H.-C. Chou were responsible for the development of the study concept and design and for the preparation of the manuscript. Ms. H.-C. Chou contributed to the data acquisition and statistical analysis. All authors participated in the analysis and interpretation of the data and read and approved the manuscript for submission.

Conflict of interests

Hsin-Chun Chou, Wen-Wen Chen, and Fei-Yuan Hsiao have no conflicts of interest that are directly relevant to the content of this study.

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Authors and Affiliations

  1. Taiwan Drug Relief Foundation, Taipei, Taiwan

    Hsin-Chun Chou & Wen-Wen Chen

  2. Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Room 220, 2F, #33, Lin-Sen S. Road, Section 1, Taipei, 10050, Taiwan

    Fei-Yuan Hsiao

  3. School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan

    Fei-Yuan Hsiao

  4. Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan

    Fei-Yuan Hsiao

Authors
  1. Hsin-Chun Chou
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  2. Wen-Wen Chen
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Correspondence to Fei-Yuan Hsiao.

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Chou, HC., Chen, WW. & Hsiao, FY. Acute Pancreatitis in Patients with Type 2 Diabetes Mellitus Treated with Dipeptidyl Peptidase-4 Inhibitors: A Population-Based Nested Case-Control Study. Drug Saf 37, 521–528 (2014). https://doi.org/10.1007/s40264-014-0171-x

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