Mamtani Ronac, Pfanzelter Nick, Haynes Kevin, Finkelman Brian S, Wang Xingmei, Keefe Stephen M, Haas Naomi B, Vaughn David J, Lewis James D
Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA
Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA.
Diabetes Care. 2014 Jul;37(7):1910-7. doi: 10.2337/dc13-1489. Epub 2014 Feb 4.
Previous studies evaluating the effect of metformin on cancer risk have been impacted by time-related biases. To avoid these biases, we examined the incidence of bladder cancer in new users of metformin and sulfonylureas (SUs).
This cohort study included 87,600 patients with type 2 diabetes in The Health Improvement Network database. Use of metformin or an SU was treated as a time-dependent variable. Cox regression-generated hazard ratios (HRs) compared metformin use with SU use, adjusted for age, sex, smoking, obesity, and HbA1c level.
We identified 196 incident bladder cancers in the metformin cohort and 66 cancers in the SU cohort. Use of metformin was not associated with decreased bladder cancer risk (HR 0.81 [95% CI 0.60-1.09]). This association did not differ by sex (P for interaction = 0.20). We observed no association with duration of metformin relative to SU use (3 to <4 years of use: 0.57 [0.25-1.34]; 4 to <5 years of use: 0.93 [0.30-2.85; ≥5 years of use: 1.18 [0.44-3.19]; P for trend = 0.26).
Use of metformin is not associated with a decreased incidence of bladder cancer. Similar methods should be used to study other cancers that have previously been identified as potentially preventable with metformin.
既往评估二甲双胍对癌症风险影响的研究受到时间相关偏倚的影响。为避免这些偏倚,我们研究了二甲双胍和磺脲类药物(SUs)新使用者的膀胱癌发病率。
这项队列研究纳入了健康改善网络数据库中的87600例2型糖尿病患者。二甲双胍或SUs的使用被视为时间依赖性变量。通过Cox回归生成风险比(HRs),比较二甲双胍与SUs的使用情况,并根据年龄、性别、吸烟、肥胖和糖化血红蛋白水平进行调整。
我们在二甲双胍队列中识别出196例新发膀胱癌,在SUs队列中识别出66例癌症。使用二甲双胍与降低膀胱癌风险无关(HR 0.81 [95%CI 0.60 - 1.09])。这种关联在性别上无差异(交互作用P值 = 0.20)。相对于SUs的使用,我们未观察到二甲双胍使用时长与膀胱癌之间的关联(使用3至<4年:0.57 [0.25 - 1.34];使用4至<5年:0.93 [0.30 - 2.85];使用≥5年:1.18 [0.44 - 3.19];趋势P值 = 0.26)。
使用二甲双胍与膀胱癌发病率降低无关。应采用类似方法研究其他先前被认为可用二甲双胍潜在预防的癌症。