雖然有研究發(fā)現(xiàn)二甲雙胍可以預(yù)防癌癥，但涉及到對(duì)象為人的研究，結(jié)果是矛盾的。因此，研究領(lǐng)導(dǎo)者Lori Sakoda博士所在的實(shí)驗(yàn)室進(jìn)行了這項(xiàng)研究，以進(jìn)一步明確二甲雙胍的使用與肺癌風(fēng)險(xiǎn)之間的關(guān)聯(lián)。
Sakoda和他的同事進(jìn)行了一項(xiàng)回顧性隊(duì)列研究，其中涉及47351名糖尿病患者（百分之54為男性），這些參與者年齡在40歲或以上，他們完成了1994年和1996年之間的健康相關(guān)調(diào)查，研究者從電子藥房記錄收集他們的糖尿病藥物信息。
在15年的隨訪研究中，747例患者被診斷為肺癌。其中，80人為不吸煙者，而203名當(dāng)前正好是吸煙者。二甲雙胍的使用與總體肺癌風(fēng)險(xiǎn)較低無(wú)關(guān)，但是，從不吸煙的糖尿病患者患肺癌的風(fēng)險(xiǎn)降低43％，并且假如二甲雙胍更長(zhǎng)使用，風(fēng)險(xiǎn)似乎降低更多。使用二甲雙胍五年或更長(zhǎng)時(shí)間的不吸煙者肺癌風(fēng)險(xiǎn)降低52％，但這一結(jié)果并沒(méi)有統(tǒng)計(jì)學(xué)顯著意義。
二甲雙胍服用五個(gè)或更多年，肺腺癌風(fēng)險(xiǎn)下降31％有關(guān)，肺腺癌是在非吸煙者中最常見(jiàn)的診斷類型，而小細(xì)胞肺癌的風(fēng)險(xiǎn)增加82％，小細(xì)胞肺癌是在吸煙者中最常見(jiàn)的診斷類型，但這些發(fā)現(xiàn)沒(méi)有統(tǒng)計(jì)學(xué)顯著意義。
Sakoda說(shuō)，雖然二甲雙胍的使用與肺癌風(fēng)險(xiǎn)無(wú)相關(guān)性，然而當(dāng)我們看所有糖尿病患者時(shí)，我們的研究結(jié)果表明，肺癌風(fēng)險(xiǎn)的差異可能是由吸煙史不同導(dǎo)致的，二甲雙胍的服用會(huì)減少非吸煙者的風(fēng)險(xiǎn)，增加吸煙者的風(fēng)險(xiǎn)。
因此還需要額外的大型，精心設(shè)計(jì)的研究，以闡明二甲雙胍是否可用于預(yù)防肺癌或其他癌癥，特別是在特定的亞群如吸煙者中。
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. .
