ABSTRACT: Background:Whether metformin may reduce the risk of uterine leiomyoma in type 2 diabetes patients has not been investigated. This retrospective cohort study compared the risk of uterine leiomyoma in ever versus never users of metformin. Methods:Female patients with new-onset type 2 diabetes during 1999-2005 were enrolled from the reimbursement database of Taiwan's National Health Insurance and followed up from 1 January 2006 until 31 December 2011. Analyses were conducted in a propensity score (PS) matched-pair cohort of 10,998 ever users and 10,998 never users of metformin. Hazard ratios were estimated by Cox regression incorporated with the inverse probability of treatment weighting using the PS. Results:A total of 321 never users and 162 ever users developed uterine leiomyoma during follow up, with respective incidence of 704.65 and 329.82 per 100,000?person-years. The overall hazard ratio was 0.467 (95% confidence interval: 0.387-0.564). The hazard ratios for the first (<23.3?months), second (23.3-53.1?months), and third (>53.1?months) tertiles of cumulative duration were 0.881 (0.685-1.132), 0.485 (0.367-0.642), and 0.198 (0.134-0.291), respectively; and were 0.751 (0.576-0.980), 0.477 (0.360-0.632), and 0.277 (0.198-0.386), respectively, for the first (<655,000?mg), second 655,000-1,725,500?mg), and third (>1,725,500) tertiles of cumulative dose. Sensitivity analyses after excluding users of sulfonylurea, users of estrogen, users of insulin, users of incretin-based therapies during follow up, patients with irregular drug refills, patients who discontinued the use of metformin, patients who received metformin prescription less than four times, or redefining uterine leiomyoma by using 'diagnostic code' plus 'procedure codes' consistently supported a lower risk of uterine leiomyoma in ever users of metformin. Conclusion:Metformin use is associated with a lower risk of uterine leiomyoma.
