This study investigated the effects of diabetes and antidiabetic medications on the risk of pancreatic cancer(PaC). We extracted data on Koreans with newly diagnosed diabetes and selected age- and sex-matched controls provided by the National Health Insurance Corporation. Incident PaC was defined as a new registration in the Korea Central Cancer Registry under ICD-10 C25 with admission history until 2015. During 19,429,617.1 person-years, 8,589 PaCs were identified in 1,005,409 subjects for diabetes group and 4,021,636 subjects for control group. The diabetes group showed more than a two-fold risk for PaC compared with the control group. Among antidiabetic medications, metformin, thiazolidinedione, and dipeptidyl peptidase-4 inhibitor exposure was associated with decreased risk for future PaC(hazard ratio[95% confidence interval] = 0.86[0.77-0.96], 0.82[0.68-0.98], 0.57[0.51-0.64], respectively), whereas sulfonylurea and insulin exposure was related to increased risk(hazard ratio[95% CI] = 1.73[1.57-1.91], 2.86[1.43-5.74], respectively) compared to subjects with no drug exposure. Moreover, subjects with dual exposure history to metformin plus thiazolidinedione or metformin plus dipeptidyl peptidase-4 inhibitor had a lower risk of PaC compared to metformin-only treated subjects. In conclusion, Korean adults with diabetes are at higher risk of PaC compared with nondiabetic individuals, and this risk may be modified by antidiabetic medications.
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