Effects of Metformin Dose on Cancer Risk Reduction in Patients with Type 2 Diabetes Mellitus: A 6-Year Follow-up Study

STUDY OBJECTIVE To explore the effects of metformin dose on cancer risk reduction in patients with type 2 diabetes. DESIGN Population-based cohort study. DATA SOURCE National Health Insurance program Longitudinal Health Insurance Database. PATIENTS A total of 65,754 age-and gender-matched patients without diabetes and no previous cancer diagnosis were extracted from the database. MEASUREMENTS AND MAIN RESULTS We compared cancer risk among the subjects who had no diabetes, had type 2 diabetes but were not on diabetes drugs, used metformin only, used antidiabetic drugs other than metformin, or used metformin in combination with other antidiabetic drugs. Our results revealed dose-dependent effects of metformin on cancer risk and cancer onset times. A significant decrease in cancer risk was found in the monotherapy group who received more than 360 defined daily doses (DDDs) of metformin (hazard ratio [HR] 0.40, 95% confidence interval [CI] 0.24-0.66). The greatest decrease in cancer risk was observed in patients who took more than 1080 DDDs (HR 0.27, 95% CI 0.09-0.84). Significantly greater dose-dependent effects were seen in patients who used metformin in combination with other antidiabetic drugs. CONCLUSION The magnitude of cancer risk reduction and prolonged cancer onset times produced by metformin in patients with type 2 diabetes depended on the dose of metformin, regardless of whether metformin was used alone or combined with other antidiabetic drugs.