Chin-Hsiao Tseng1,2,3. 1. Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan. 2. Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. 3. Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Taiwan.
Abstract
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.
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.