Metformin Use and the Risk of Cancer in Patients with Diabetes: A Nationwide Sample Cohort Study

Metformin is known to have an antitumor effect; however, its effects in the prevention of cancer remain controversial. This study aimed to investigate the association of metformin therapy with the development of cancer. A population-based cohort study was conducted among adult patients with diabetes in 2010 using sample cohort data from the National Health Insurance Service. Metformin users were defined as those who had been prescribed repeated oral metformin administration over a period of >= 90 days. The primary endpoint of this study was the new development of cancer from January 1, 2011, to December 31, 2015. A total of 66,627 adult patients with diabetes were included in the final analysis; 29,974 were metformin users and 36,653 were controls. In the time-dependent Cox regression model, after multivariable adjustment, the risk for the development of cancer among metformin users was not significantly different from that among controls (HR = 0.96; 95% confidence interval, 0.89-1.03; P = 0.250). In the sensitivity analysis, neither low daily dosage (<= 1 g/day, P = 0.301) nor high daily dosage (>1 g/day, P = 0.497) of metformin was significantly associated with the development of cancer between 2011 and 2015. We found no association between metformin therapy and the risk of cancer among patients with diabetes, even in the high daily dosage groups of metformin (>1 g/day). However, there might be residual confounders or bias; thus, further prospective, large population-based cohort studies are needed to confirm these findings. Impact: This population-based cohort study suggested a lack of association between metformin therapy and the risk of cancer among patients with diabetes. Therefore, the relationship between metformin therapy and the risk of cancer is still controversial.