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Nationwide Trends in Pancreatitis and Pancreatic Cancer Risk Among Patients With Newly Diagnosed Type 2 Diabetes Receiving Dipeptidyl Peptidase 4 Inhibitors

 Minyoung Lee  ;  Jiyu Sun  ;  Minkyung Han  ;  Yongin Cho  ;  Ji-Yeon Lee  ;  Chung Mo Nam  ;  Eun Seok Kang 
 DIABETES CARE, Vol.42(11) : 2057-2064, 2019 
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OBJECTIVE: Dipeptidyl peptidase 4 inhibitors (DPP-4i) are useful incretin-based antidiabetes drugs. However, there is a concern that DPP-4i may adversely impact the exocrine pancreas, owing to their pleiotropic effects. In this study, we investigated whether DPP-4i are associated with pancreatitis and pancreatic cancer using a nationwide population-based cohort study. RESEARCH DESIGN AND METHODS: We included patients newly diagnosed with type 2 diabetes who were treated with antidiabetes drugs (n = 33,208) from 2007 to 2013. The data were obtained from the Korean National Health Insurance Service-Health Screening Cohort database (n = 514,866). Risk was estimated using a Cox proportional hazards model with time-dependent covariates. A 6-month lag time was used to account for a possible latency time. The risk across various time segments since the first prescription of DPP-4i was also analyzed. RESULTS: Out of 33,208 subjects, 10,218 were new users of DPP-4i and 22,990 were new users of other antidiabetes drugs. DPP-4i significantly increased the risks of pancreatitis (adjusted hazard ratio [aHR] 1.24, 95% CI 1.01-1.52; P = 0.037) and pancreatic cancer (aHR 1.81, 95% CI 1.16-2.82; P = 0.009) with a 6-month drug use lag period. The risk of pancreatitis and pancreatic cancer was generally consistent in the first 12 months and 1 year after the initial prescription without showing an increasing trend according to exposure duration. CONCLUSIONS: DPP-4i use is associated with increased risks of pancreatitis and pancreatic cancer in patients with newly diagnosed type 2 diabetes. However, the absence of increasing trend according to exposure duration suggests the chances of reverse causality, and long-term pancreatic safety of DPP-4i has to be further investigated.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Preventive Medicine and Public Health (예방의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biomedical Systems Informatics (의생명시스템정보학교실) > 1. Journal Papers
Yonsei Authors
Kang, Eun Seok(강은석) ORCID logo https://orcid.org/0000-0002-0364-4675
Nam, Chung Mo(남정모) ORCID logo https://orcid.org/0000-0003-0985-0928
Lee, Minyoung(이민영) ORCID logo https://orcid.org/0000-0002-9333-7512
Lee, Ji Yeon(이지연)
Cho, Yong In(조용인) ORCID logo https://orcid.org/0000-0002-4645-816X
Han, Minkyung(한민경) ORCID logo https://orcid.org/0000-0002-5011-5557
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