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.
Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Division of Environmental Health and Occupational Medicine of the National Health Research Institutes, Zhunan, Taiwan. Electronic address: ccktsh@ms6.hinet.net.
Chin-Hsiao
CH
Tseng
D016022:Case-Control Studies; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000453:epidemiology*; D004305:Dose-Response Relationship, Drug; D016889:Endometrial Neoplasms / Q000453:epidemiology*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D015994:Incidence; D008687:Metformin / Q000008:administration & dosage*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D013624:Taiwan / Q000453:epidemiology
D007004:Hypoglycemic Agents; D008687:Metformin
Diabetes; Dose–response; Endometrial cancer; Epidemiology; Metformin; Taiwan