Metformin Use May Increase Risk of Pancreatic Cancer in Diabetic Women: An Analysis of the Korean National Health Insurance Service-National Health Screening Cohort Database

Background: In addition to its antidiabetic effects, metformin has pleiotropic effects, such as the inhibition of carcinogenesis. This study aimed to investigate the association between metformin use and pancreatic cancer risk in the Korean National Health Insurance Service (NHIS)-National Health Screening Cohort (HEALS). Methods: Of the individuals in the Korean NHIS-HEALS, 29,271 men and 19,091 women were included in the final analysis after propensity score matching based on age, body mass index, and smoking status. The study population was categorized into three groups: metformin non-users with diabetes mellitus (DM), metformin users with DM, and non-diabetic users. A Cox proportional hazards regression model was used to examine the association between metformin use and pancreatic cancer. Results: The median follow-up period was 12.9 years. The estimated pancreatic cancer incidence was highest in metformin users with DM, regardless of sex (P<0.001), and lowest in non-diabetic men and female metformin nonusers (P=0.053). The hazard ratios (95% confidence interval) for pancreatic cancer incidence in metformin users and non-diabetic individuals were 1.116 (0.648–1.923) and 0.447 (0.259–0.771) in men and 2.769 (1.003–7.642) and 1.451 (0.529–3.984) in women, respectively, after full adjustment. Conclusion: Women with diabetes using metformin are at a higher risk of pancreatic cancer than women with diabetes not using metformin. Meanwhile, men with DM using metformin have a similar risk of pancreatic cancer as men with DM not using metformin.