Incidence and Survival Outcomes of Colorectal Cancer in Long-Term Metformin Users with Diabetes: A Population-Based Cohort Study Using a Common Data Model

Background and aims: Previous studies have reported that metformin use in patients with diabetes mellitus may reduce the risk of colorectal cancer (CRC) incidence and prognosis; however, the evidence is not definite. This population-based cohort study aimed to investigate whether metformin reduces the risk of CRC incidence and prognosis in patients with diabetes mellitus using a common data model of the Korean National Health Insurance Service database from 2002 to 2013. Methods: Patients who used metformin for at least 6 months were defined as metformin users. The primary outcome was CRC incidence, and the secondary outcomes were the all-cause and CRC-specific mortality. Cox proportional hazard model was performed and large-scaled propensity score matching was used to control for potential confounding factors. Results: During the follow-up period of 81,738 person-years, the incidence rates (per 1000 person-years) of CRC were 5.18 and 8.12 in metformin users and non-users, respectively (p = 0.001). In the propensity score matched cohort, the risk of CRC incidence in metformin users was significantly lower than in non-users (hazard ratio (HR), 0.58; 95% CI (confidence interval), 0.47-0.71). In the sensitivity analysis, the lag period extending to 1 year showed similar results (HR: 0.63, 95% CI: 0.51-0.79). The all-cause mortality was significantly lower in metformin users than in non-users (HR: 0.71, 95% CI: 0.64-0.78); CRC-related mortality was also lower among metformin users. However, there was no significant difference (HR: 0.55, 95% CI: 0.26-1.08). Conclusions: Metformin use was associated with a reduced risk of CRC incidence and improved overall survival.