Metformin use and risk of cancer in patients with type 2 diabetes: a cohort study of primary care records using inverse probability weighting of marginal structural models
Metformin use and risk of cancer in patients with type 2 diabetes: a cohort study of primary care records using inverse probability weighting of marginal structural models
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DOI：
10.1093/ije/dyz005
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发表时间：
2019-04-01
影响因子：
7.7
通讯作者：
Bhaskaran, Krishnan
中科院分区：
文献类型：
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作者：
Farmer, Ruth E.;Ford, Deborah;Bhaskaran, Krishnan
背景：先前的研究提供了关于二甲双胍是否具有抗癌作用的相互矛盾的证据。在研究二甲双胍暴露量随时间变化时，协变量如体重指数（BMI）和糖化血红蛋白（HbA 1c）可能既是混杂因素，也是因果途径变量，因此无法通过标准回归方法进行充分处理。具有治疗权重逆概率（IPTW）的边缘结构模型（MSM）可以正确调整此类混杂因素。使用这种方法，本研究的主要目的是估计二甲双胍对癌症风险的影响相比，风险与T2 DM患者服用nothingmedication.Methods：事件2型糖尿病（T2 DM）患者被确定在临床实践研究数据链（CPRD），电子健康记录数据库来自初级保健在英国。患者在糖尿病诊断时或之后的第一个时间点进入研究，此时他们具有有效的HbA 1c和BMI测量值，并且随访分为1个月的间隔。Logistic回归计算IPTW，然后计算二甲双胍对所有癌症的影响（包括和不包括非黑色素瘤皮肤癌）和乳腺癌、前列腺癌、肺癌、结直肠癌和胰腺癌在加权population.Results中进行估计：总共55629例T2 DM患者在他们的研究进入时存活并且无癌症;在中位随访时间2.9年[四分位距（IQR）1.3-5.4年]期间，有2530人患上了癌症。使用MSM方法，与二甲双胍治疗相比，所有癌症的风险比（HR）为1.02（0.88-1.18）。结果对一系列敏感性分析具有稳健性，并且在根据暴露时长估计治疗效应时保持一致。我们也没有发现二甲双胍对个体癌症预后有保护作用的证据。结论：我们没有发现二甲双胍与癌症风险有因果关系的证据。
Background: Previous studies provide conflicting evidence on whether metformin is protective against cancer. When studying time-varying exposure to metformin, covariates such as body mass index (BMI) and glycated haemoglobin (HbA1c) may act as both confounders and causal pathway variables, and so cannot be handled adequately by standard regression methods. Marginal structural models (MSMs) with inverse probability of treatment weights (IPTW) can correctly adjust for such confounders. Using this approach, the main objective of this study was to estimate the effect of metformin on cancer risk compared with risk in patients with T2DM taking no medication.Methods: Patients with incident type 2 diabetes (T2DM) were identified in the Clinical Practice Research Datalink (CPRD), a database of electronic health records derived from primary care in the UK. Patients entered the study at diabetes diagnosis or the first point after this when they had valid HbA1c and BMI measurements, and follow-up was split into 1-month intervals. Logistic regression was used to calculate IPTW; then the effect of metformin on all cancers (including and excluding non-melanoma skin cancer) and breast, prostate, lung, colorectal and pancreatic cancers was estimated in the weighted population.Results: A total of 55 629 T2DM patients were alive and cancer-free at their study entry; 2530 people had incident cancer during a median follow-up time of 2.9 years [interquartile range (IQR) 1.3-5.4 years]. Using the MSM approach, the hazard ratio (HR) for all cancers, comparing treatment with metformin with no glucose-lowering treatment, was 1.02 (0.88-1.18). Results were robust to a range of sensitivity analyses and remained consistent when estimating the treatment effect by length of exposure. We also found no evidence of a protective effect of metformin on individual cancer outcomes.Conclusions: We find no evidence that metformin has a causal association with cancer risk.