Dose-Dependent Relationship Between Metformin and Colorectal Cancer Occurrence Among Patients with Type 2 Diabetes-A Nationwide Cohort Study
Dose-Dependent Relationship Between Metformin and Colorectal Cancer Occurrence Among Patients with Type 2 Diabetes-A Nationwide Cohort Study
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DOI：
10.1016/j.tranon.2018.02.012
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发表时间：
2018-04-01
影响因子：
5
通讯作者：
Wang, Jaw-Yuan
中科院分区：
文献类型：
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作者：
Chang, Yu-Tang;Tsai, Hsiang-Lin;Wang, Jaw-Yuan
背景技术背景：越来越多的证据表明，二甲双胍可能有利于结直肠癌（CRC）的一级预防，并已报告了剂量-反应关系。然而，很少报告二甲双胍治疗期间、累积剂量和强度与CRC之间的长期流行病学观察结果。本研究的目的是确定二甲双胍和CRC的发展之间的关系，在全国范围内的队列study.METHODS：这个全国范围内的人口为基础的研究检查了一个队列的100万例患者随机抽样的个人登记在台湾全民健康保险系统。入选了1997年至2007年间新诊断的2型糖尿病（DM）患者。一个统计变量，包括人口统计学数据，治疗期间，累积剂量，二甲双胍的使用强度，发生CRC和那些没有CRC的患者之间进行了比较。平均随访时间为7.17 ± 3.21年。调整后，二甲双胍的使用是防止结直肠癌发展的独立保护因素（P <0.001）。虽然二甲双胍对结直肠癌发展的保护能力在长期治疗过程中降低，但结直肠癌的风险随着二甲双胍使用的累积剂量或强度的增加而逐渐降低（均P <.001）。结论：本研究显示，二甲双胍的使用以剂量依赖的方式显著降低了台湾人群中2型糖尿病患者的结直肠癌风险。然而，药物依从性的逐渐下降可能会降低二甲双胍在长期治疗期间对CRC发展的保护能力。
BACKGROUND: Increasing bodies of evidence suggest that metformin may be beneficial in the primary prevention of colorectal cancer (CRC), and a dose-response relationship has been reported. However, long-term epidemiological observations between the treatment period, cumulative dose, and intensity of metformin and CRC are rarely reported. The aim of this study was to identify the association between the effect of metformin and CRC development in a nationwide cohort study.METHODS: This nationwide population-based study examined a cohort of 1,000,000 patients randomly sampled from individuals enrolled in the Taiwan National Health Insurance system. Patients with newly diagnosed type 2 diabetes mellitus (DM) between 1997 and 2007 were enrolled. A statistical variables, including the demographic data, treatment period, cumulative dose, and intensity of metformin use, was compared between patients developing CRC and those without CRC.RESULTS: This study included 47,597 patients. The mean follow-time was 7.17 +/- 3.21 years. After adjustment, metformin use was an independent protective factor against CRC development (P < .001). Although the protective ability of metformin against CRC development was reduced during long-term therapy, the risk of CRC decreased progressively with a higher cumulative dose or higher intensity of metformin use (both P < .001).CONCLUSION: This study revealed that metformin use significantly reduced the risk of CRC in a dose-dependent manner in patients with type 2 DM in the Taiwanese population. However, a gradual decline in medication adherence may reduce the protective ability of metformin against CRC development during long-term therapy.