Metformin reduces ovarian cancer risk in Taiwanese women with type 2 diabetes mellitus

BACKGROUND: Whether metformin therapy affects ovarian cancer risk in Asian patients with type 2 diabetes mellitus has not been investigated. METHODS: Data analysis was performed in 2014. The reimbursement databases of Taiwanese female patients with a new diagnosis of type 2 diabetes mellitus between 1998 and 2002 (n = 479,475) were retrieved from the National Health Insurance for follow-up of ovarian cancer until the end of 2009. Metformin was treated as a time-dependent variable; and of these patients, 286,106 were never-users, and 193,369 were ever-users. A time-dependent approach was used to calculate ovarian cancer incidence and estimate hazard ratios by Cox regression for never-users (as referent group), ever-users and subgroups of metformin exposure (tertiles of cumulative duration and cumulative dose). RESULTS: During follow-up, 601 metformin ever-users and 2600 never-users developed ovarian cancer, representing an incidence of 49.4 and 146.4 per 100,000 person-years, respectively. The overall fully adjusted hazard ratio (95% confidence intervals) for ever-users versus never-users was 0.658 (0.593-0.730). The fully adjusted hazard ratios for the first, second and third tertiles of cumulative duration of metformin therapy were 1.169 (1.019-1.341), 0.761 (0.644-0.898) and 0.276 (0.225-0.340), respectively (p trend < 0.01) and 1.220 (1.067-1.395), 0.610 (0.513-0.725) and 0.305 (0.248-0.374), respectively (p trend < 0.01), for a cumulative dose of metformin. In additional analyses, sulfonylureas but not the other antidiabetic drugs were associated with a reduced risk of ovarian cancer. CONCLUSIONS: Metformin use is associated with a decreased risk of ovarian cancer.