Metformin and endometrial cancer risk in Chinese women with type 2 diabetes mellitus in Taiwan.

Objective: To evaluate metformin effects on endometrial cancer risk in Chinese female patients with type 2 diabetes mellitus (T2DM) in Taiwan.

Methods: This is a retrospective cohort analysis using the National Health Insurance database of Taiwan. Female patients with newly diagnosed T2DM and without endometrial cancer in 1998-2002 were followed to end of 2009 (n=478,921). Among them, 285,916 were never-users and 193,005 were ever-users of metformin. A time-dependent approach was used to calculate endometrial cancer incidence and estimate hazard ratios by Cox regression for ever-users, never-users, and subgroups of metformin exposure (tertiles of cumulative duration and cumulative dose). Sensitivity analyses were conducted in various subgroups.

Results: During follow-up, 728 metformin ever-users and 2157 never-users developed endometrial cancer, representing an incidence of 60.00 and 121.69 per 100,000 person-years, respectively. The overall hazard ratio (95% confidence intervals) for ever- versus never-users after adjustment for propensity score (PS) was 0.675 (0.614-0.742). The PS-adjusted hazard ratios for the first, second, and third tertiles of cumulative duration of metformin therapy were 1.089 (0.966-1.228), 0.707 (0.616-0.812) and 0.313 (0.262-0.374), respectively (P-trend<0.0001); and 1.062 (0.942-1.197), 0.620 (0.538-0.715) and 0.376 (0.317-0.447), respectively (P-trend<0.0001), for cumulative dose of metformin. The dose-response relationship was demonstrated in various models and an overall reduced risk was consistently supported by sensitivity analyses.

Conclusions: The use of metformin in women with T2DM was associated with an overall significantly lower risk of endometrial cancer with dose-response relationship.