Tufts Medical Center, 800 Washington Street, Box 245, Boston, MA 02111, USA.
Cancer Epidemiol. 2013 Oct;37(5):742-9. doi: 10.1016/j.canep.2013.04.015. Epub 2013 Jun 15.
Observational studies have associated metformin use with lower colorectal cancer (CRC) incidence but few studies have examined metformin's influence on CRC survival. We examined the relationships among metformin use, diabetes, and survival in postmenopausal women with CRC in the Women's Health Initiative (WHI) clinical trials and observational study.
2066 postmenopausal women with CRC were followed for a median of 4.1 years, with 589 deaths after CRC diagnosis from all causes and 414 deaths directly attributed to CRC. CRC-specific survival was compared among women with diabetes with metformin use (n=84); women with diabetes with no metformin use (n=128); and women without diabetes (n=1854). Cox proportional hazard models were used to estimate associations among metformin use, diabetes and survival after CRC. Strategies to adjust for potential confounders included: multivariate adjustment with known predictors of colorectal cancer survival and construction of a propensity score for the likelihood of receiving metformin, with model stratification by propensity score quintile.
After adjusting for age and stage, CRC specific survival in women with diabetes with metformin use was not significantly different compared to that in women with diabetes with no metformin use (HR 0.75; 95% CI 0.40-1.38, p=0.67) and to women without diabetes (HR 1.00; 95% CI 0.61-1.66, p=0.99). Following propensity score adjustment, the HR for CRC-specific survival in women with diabetes with metformin use compared to non-users was 0.78 (95% CI 0.38-1.55, p=0.47) and for overall survival was 0.86 (95% CI 0.49-1.52; p=0.60).
In postmenopausal women with CRC and DM, no statistically significant difference was seen in CRC specific survival in those who used metformin compared to non-users. Analyses in larger populations of colorectal cancer patients are warranted.
观察性研究表明，使用二甲双胍与结直肠癌（CRC）发病率降低相关，但很少有研究检查二甲双胍对 CRC 生存的影响。我们在妇女健康倡议（WHI）临床试验和观察研究中检查了使用二甲双胍的糖尿病与 CRC 后生存之间的关系。
2066 名绝经后 CRC 患者中位随访 4.1 年，CRC 诊断后共有 589 例患者因各种原因死亡，414 例患者因 CRC 直接死亡。比较了患有糖尿病且使用二甲双胍的患者（n=84）；患有糖尿病且未使用二甲双胍的患者（n=128）；以及无糖尿病的患者（n=1854）之间的 CRC 特异性生存。使用 Cox 比例风险模型估计使用二甲双胍、糖尿病与 CRC 后生存之间的关联。调整潜在混杂因素的策略包括：多变量调整结直肠癌生存的已知预测因素，并构建接受二甲双胍治疗可能性的倾向评分，通过倾向评分五分位数进行模型分层。
在调整年龄和分期后，患有糖尿病且使用二甲双胍的患者的 CRC 特异性生存率与未使用二甲双胍的患者（HR 0.75；95%CI 0.40-1.38，p=0.67）和无糖尿病的患者（HR 1.00；95%CI 0.61-1.66，p=0.99）无显著差异。在倾向评分调整后，与非使用者相比，患有糖尿病且使用二甲双胍的患者的 CRC 特异性生存率 HR 为 0.78（95%CI 0.38-1.55，p=0.47），总生存率 HR 为 0.86（95%CI 0.49-1.52；p=0.60）。
在患有 CRC 和 DM 的绝经后妇女中，使用二甲双胍的患者与未使用者相比，CRC 特异性生存率无统计学差异。需要在更大的结直肠癌患者人群中进行分析。
