虽然有研究发现二甲双胍可以预防癌症，但涉及到对象为人的研究，结果是矛盾的。因此，研究领导者Lori Sakoda博士所在的实验室进行了这项研究，以进一步明确二甲双胍的使用与肺癌风险之间的关联。
Sakoda和他的同事进行了一项回顾性队列研究，其中涉及47351名糖尿病患者（百分之54为男性），这些参与者年龄在40岁或以上，他们完成了1994年和1996年之间的健康相关调查，研究者从电子药房记录收集他们的糖尿病药物信息。
在15年的随访研究中，747例患者被诊断为肺癌。其中，80人为不吸烟者，而203名当前正好是吸烟者。二甲双胍的使用与总体肺癌风险较低无关，但是，从不吸烟的糖尿病患者患肺癌的风险降低43％，并且假如二甲双胍更长使用，风险似乎降低更多。使用二甲双胍五年或更长时间的不吸烟者肺癌风险降低52％，但这一结果并没有统计学显著意义。
二甲双胍服用五个或更多年，肺腺癌风险下降31％有关，肺腺癌是在非吸烟者中最常见的诊断类型，而小细胞肺癌的风险增加82％，小细胞肺癌是在吸烟者中最常见的诊断类型，但这些发现没有统计学显著意义。
Sakoda说，虽然二甲双胍的使用与肺癌风险无相关性，然而当我们看所有糖尿病患者时，我们的研究结果表明，肺癌风险的差异可能是由吸烟史不同导致的，二甲双胍的服用会减少非吸烟者的风险，增加吸烟者的风险。
因此还需要额外的大型，精心设计的研究，以阐明二甲双胍是否可用于预防肺癌或其他癌症，特别是在特定的亚群如吸烟者中。
doi:10.1158/1940-6207.CAPR-14-0291
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Metformin Use and Lung Cancer Risk in Patients with Diabetes
Lori C. Sakoda*, Assiamira Ferrara, Ninah S. Achacoso, Tiffany Peng, Samantha F. Ehrlich, Charles P. Quesenberry, Jr, and Laurel A. Habel
Methodologic biases may explain why observational studies examining metformin use in relation to lung cancer risk have produced inconsistent results. We conducted a cohort study to further investigate this relationship, accounting for potential biases. For 47,351 patients with diabetes ages ≥40 years, who completed a health-related survey administered between 1994 and 1996, data on prescribed diabetes medications were obtained from electronic pharmacy records. Follow-up for incident lung cancer occurred from January 1, 1997, until June 30, 2012. Using Cox regression, we estimated lung cancer risk associated with new use of metformin, along with total duration, recency, and cumulative dose (all modeled as time-dependent covariates), adjusting for potential confounding factors. During 428,557 person-years of follow-up, 747 patients were diagnosed with lung cancer. No association was found with duration, dose, or recency of metformin use and overall lung cancer risk. Among never smokers, however, ever use was inversely associated with lung cancer risk [HR, 0.57; 95% confidence interval (CI), 0.33–0.99], and risk appeared to decrease monotonically with longer use (≥5 years: HR, 0.48; 95% CI, 0.21–1.09). Among current smokers, corresponding risk estimates were >1.0, although not statistically significant. Consistent with this variation in effect by smoking history, longer use was suggestively associated with lower adenocarcinoma risk (HR, 0.69; 95% CI, 0.40–1.17), but higher small cell carcinoma risk (HR, 1.82; 95% CI, 0.85–3.91). In this population, we found no evidence that metformin use affects overall lung cancer risk. The observed variation in association by smoking history and histology requires further confirmation. .
