Metformin may reduce bladder cancer risk in Taiwanese patients with type 2 diabetes

Whether metformin therapy affects bladder cancer risk in patients with type 2 diabetes mellitus (T2DM) has not been extensively investigated. The reimbursement databases of all Taiwanese patients with a new diagnosis of T2DM between 1998 and 2002 (n = 940,708) were retrieved from the National Health Insurance for follow-up of bladder cancer up to the end of 2009. Metformin was treated as a time-dependent variable, and of these patients, 532,519 were never-users and 408,189 were ever-users of metformin. A time-dependent approach was applied in the calculation of bladder cancer incidence and in the estimation of hazard ratios by Cox regression for ever-users, never-users, and subgroups of metformin exposure (using tertile cutoffs of cumulative duration of therapy and cumulative dose). During the study period, 1,847 (0.45%) metformin ever-users and 6,213 (1.17%) metformin never-users developed bladder cancer, representing an incidence of 72.03 and 189.22 per 100,000 person-years, respectively. The age-sex-adjusted and multivariable-adjusted hazard ratios (95% confidence intervals) for ever- versus never-users were 0.382 (0.360-0.405) and 0.600 (0.564-0.638), respectively. The multivariable-adjusted hazard ratios for the first, second, and third tertiles of cumulative duration of metformin therapy were 1.034 (0.954-1.120), 0.696 (0.632-0.766), and 0.258 (0.229-0.291), respectively (P trend <0.0001). Similarly, the multivariable-adjusted hazard ratios for the first, second, and third tertiles of cumulative dose of metformin were 0.997 (0.920-1.080), 0.615 (0.559-0.677), and 0.285 (0.253-0.321), respectively (P trend <0.0001). This study suggests that metformin use is associated with a decreased risk of bladder cancer in patients with T2DM.