Southern California Permanente Medical Group, Department of Research & Evaluation, Pasadena, California , USA.
Division of Medical Oncology and Hematology , Harbor-UCLA Medical Center , Torrance, California , USA.
BMJ Open Diabetes Res Care. 2015 Jan 24;3(1):e000049. doi: 10.1136/bmjdrc-2014-000049. eCollection 2015.
We investigated if metformin lowers breast, endometrial, and ovarian cancer risk in women with type 2 diabetes mellitus compared with women who used other antidiabetic medications.
We followed a cohort of 66 778 female patients with diabetes for a maximum of 12 years (median 6 years). We examined breast, endometrial, and ovarian cancer risk, and the composite cancer risk. We examined drug categories using pharmacy records: metformin only; metformin combination regimens; non-metformin regimens; and non-users. We used χ(2) analyses to examine categorical variables. We conducted multivariable Cox regression models with time-dependent drug use status.
Women who used metformin combination regimens versus metformin only had a 15% lower breast cancer risk (adjusted HR=0.85, 95% CI 0.69 to 1.04). After stratifying by glycated hemoglobin (HbA1c), the association attenuated in those who had poorly controlled HbA1c (adjusted HR=1.06, 95% CI 0.73 to 1.55). Given the small numbers of ovarian and endometrial cancer outcomes, we examined these as a composite. The risk of all cancers combined was similar in those who used metformin combination regimens versus metformin only (adjusted HR=0.92, 95% CI 0.78 to 1.10). We found no significant differences for breast cancer or all cancers combined when we compared risks in non-metformin users versus metformin only users.
Women who used metformin and other antidiabetic drugs had a lower breast cancer risk compared with women who used metformin only, but the results were not significant. We also found no difference in overall cancer risks when we compared women who used other antidiabetic drugs (no metformin) versus metformin users.
我们研究了与使用其他抗糖尿病药物的女性相比，二甲双胍是否降低了 2 型糖尿病女性的乳腺癌、子宫内膜癌和卵巢癌风险。
我们对 66778 名患有糖尿病的女性患者进行了最多 12 年（中位 6 年）的随访。我们检查了乳腺癌、子宫内膜癌和卵巢癌风险以及复合癌症风险。我们使用药房记录检查了药物类别：仅二甲双胍；二甲双胍联合治疗方案；非二甲双胍方案；和未使用者。我们使用 χ(2)分析检查了分类变量。我们使用具有时间依赖性药物使用状态的多变量 Cox 回归模型进行了分析。
与仅使用二甲双胍的女性相比，使用二甲双胍联合治疗方案的女性乳腺癌风险降低了 15%（调整后的 HR=0.85，95%CI 0.69 至 1.04）。在根据糖化血红蛋白（HbA1c）分层后，HbA1c 控制不佳的患者（调整后的 HR=1.06，95%CI 0.73 至 1.55）的相关性减弱。鉴于卵巢癌和子宫内膜癌结局的数量较少，我们将其作为一个组合进行了检查。使用二甲双胍联合治疗方案的女性与仅使用二甲双胍的女性相比，所有癌症的综合风险相似（调整后的 HR=0.92，95%CI 0.78 至 1.10）。当我们比较非二甲双胍使用者与仅使用二甲双胍使用者的风险时，我们没有发现乳腺癌或所有癌症的综合风险存在显著差异。
与仅使用二甲双胍的女性相比，使用二甲双胍和其他抗糖尿病药物的女性乳腺癌风险较低，但结果无统计学意义。当我们比较使用其他抗糖尿病药物（无二甲双胍）与使用二甲双胍的女性的总体癌症风险时，我们也没有发现差异。
