二甲双胍预防2型糖尿病患者发生结直肠癌的马尔科夫模型分析

Effect of metformin on colorectal carcinoma in type 2 diabetes mellitus patients： a Markov model analysis

目的 通过构建马尔科夫决策模型，评估二甲双胍对2型糖尿病患者（T2DM）发生结直肠癌风险的预防作用。方法 通过PubMed及Cochrane Library数据库，对2010年9月至2016年12月发表的服用二甲双胍及服用其他治疗糖尿病药物的T2DM患者结直肠癌发生率相关的文献进行检索，纳入标准为：研究人群为无结直肠癌的T2DM成年患者，研究为随机对照试验、半随机对照试验或前瞻性或回顾性队列研究，构建模型所需的参数在研究中有报道。提取参数构建马尔科夫决策模型，模型观察终点为结直肠癌的发生率。比较无结直肠癌的T2DM患者服用与不服用二甲双胍患者在设定的11年随访周期后的结直肠癌发生率及累计无瘤生存时间，并采用二阶蒙特卡洛概率灵敏度分析方法对模型结果产生的影响进行评估。结果 共纳入7篇符合要求的文献，通过模拟二甲双胍治疗和非二甲双胍治疗两组方案各入组10 000例患者。与非二甲双胍治疗组相比，二甲双胍治疗组的T2DM患者结直肠癌发生率更低（1.670%比2.146%），差异有统计学意义（P= 0.016）。二甲双胍治疗组的累计无瘤生存时间10.908年，非二甲双胍治疗组10.882年，差异有统计学意义（P= 0.000）。结论 服用二甲双胍或可降低2型糖尿病患者的结直肠癌发生率，延长累计无瘤生存时间。

Objective To evaluate the colorectal cancer （CRC） prevention effect of metformin in comparison with that of other T2DM medications from a Markov model perspective.Methods Literature concerning CRC morbidity of T2DM patients with metformin or other diabetes medications treatment was reviewed in PubMed and Cochrane Library database from September 2010 to December 2016. Inclusion criteria： （1） enrolled population was adult patients with T2DM but without CRC; （2） any of the parameters applied in our model was reported; （3） randomized clinical trials （RCTs） , quasi-randomized trials, prospective or retrospective cohort studies. With CRC morbidity as endpoint, parameters were extracted to construct Markov model to assess CRC morbidity and cumulative tumor-free survival in each group over 11 years′ follow-up period. Finally, Monte Carlo analysis was performed to evaluate the influence of parameter instability on the model.Results Seven literatures were recruited and 10 000 patients were virtually allocated for each arm. In contrast with non-metformin group, T2DM patients treated with metformin had a lower rate of CRC （1.670% vs. 2.146%, P= 0.016） . Moreover, cumulative tumor-free survival of metformin group was, slightly but significantly, better than that of non-metformin group （10.908 years vs. 10.882 years, P= 0.000） .Conclusions T2DM patients treated with metformin have a lower morbidity of CRC and a better cumulative tumor-free survival than those of non-metformin group. Large scale RCTs are needed to illustrate the role of metformin in the prevention of CRC.