Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada.
Diabetes Care. 2013 Jan;36(1):124-9. doi: 10.2337/dc12-0740. Epub 2012 Aug 24.
Observational studies have associated metformin use with a decreased risk of lung cancer incidence in patients with type 2 diabetes, but the studies had important methodological shortcomings. The objective of this study was to determine whether metformin use is associated with a decreased risk of lung cancer in patients with type 2 diabetes, while avoiding previous biases.
Using the U.K. General Practice Research Database, we assembled a cohort of patients newly treated with oral hypoglycemic agents (OHAs) between 1988 and 2009. A nested case-control analysis was conducted, where case subjects with lung cancer occurring during follow-up were matched with up to 10 control subjects for age, sex, calendar time, and duration of follow-up. Conditional logistic regression was used to estimate adjusted rate ratios of lung cancer associated with ever use of metformin, along with measures of duration and cumulative dose. Models were adjusted for potential confounders, which included smoking.
The cohort included 115,923 new users of OHAs, with 1,061 patients diagnosed with lung cancer during follow-up (rate 2.0/1,000 person-years). Metformin use was not associated with a decreased rate of lung cancer (rate ratio 0.94 [95% CI 0.76-1.17]). No dose-response was observed by number of prescriptions received, cumulative duration of use, and dose.
Metformin use is not associated with a decreased risk of lung cancer in patients with type 2 diabetes. The decreased risk reported in other observational studies is likely due to bias from methodological shortcomings. Nonetheless, greater consideration should be given to clarify inconsistencies between experimental models and population studies.
观察性研究表明，二甲双胍的使用与 2 型糖尿病患者肺癌发病率的降低有关，但这些研究存在重要的方法学缺陷。本研究旨在确定二甲双胍的使用是否与 2 型糖尿病患者的肺癌风险降低有关，同时避免先前的偏倚。
我们使用英国全科医生研究数据库，组建了一个 1988 年至 2009 年期间新接受口服降糖药（OHA）治疗的患者队列。进行了巢式病例对照分析，其中在随访期间发生肺癌的病例患者与最多 10 名年龄、性别、日历时间和随访时间匹配的对照患者进行配对。使用条件逻辑回归估计与二甲双胍的使用相关的肺癌的调整后比值比，以及使用时间和累积剂量的措施。模型调整了潜在的混杂因素，包括吸烟。
该队列包括 115923 名新使用 OHA 的患者，其中有 1061 名患者在随访期间被诊断为肺癌（发生率为 2.0/1000 人年）。二甲双胍的使用与肺癌的发生率降低无关（比值比 0.94 [95%CI 0.76-1.17]）。通过收到的处方数量、使用的累积持续时间和剂量观察到没有剂量反应。
在 2 型糖尿病患者中，二甲双胍的使用与肺癌风险的降低无关。其他观察性研究报告的风险降低可能是由于方法学缺陷导致的偏倚。尽管如此，应更加重视阐明实验模型和人群研究之间的不一致之处。
