Kim Hae Jin, Lee SooJin, Chun Ki Hong, Jeon Ja Young, Han Seung Jin, Kim Dae Jung, Kim Young Seol, Woo Jeong-Taek, Nam Moon-Suk, Baik Sei Hyun, Ahn Kyu Jeung, Lee Kwan Woo
Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon Health Administration, Department of Management & Administration, Baekseok Arts University, Seoul Department of Preventive Medicine and Public Health, Ajou University School of Medicine, Suwon Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine, Seoul Department of Internal Medicine, Inha University College of Medicine, Incheon Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
Medicine (Baltimore). 2018 Feb;97(8):e0036. doi: 10.1097/MD.0000000000010036.
The epidemiological literature suggests that insulin resistance, hyperinsulinemia, and increased levels of insulin-like growth factors place patients with type 2 diabetes mellitus (T2DM) at greater risk of cancer. The association between cancer incidence and the use of antidiabetic medications in patients with T2DM has been recently examined. There have been conflicting reports regarding an association between metformin and cancer risk. The aim of this study was to investigate the relationship between metformin use and the incidence of cancer in Koreans with T2DM.Data from The Korean National Diabetes Program (KNDP, 2006-2014), a nationwide, large-scale, prospective, multicenter cohort study in Korea, were used to study patients with T2DM. Patients ≥30 years old whose complete medical records were available were included in this study. Patients with a history of any cancer on KNDP registration or those who had been diagnosed with any type of cancer within 1 year of metformin use were excluded. Survival curves with respect to the incidence of cancer were plotted using the Kaplan-Meier method. Hazard ratios and 95% confidence intervals for cancer were estimated in a Cox proportional hazards regression analysis.During a mean 5.8 years of follow-up, 164 of the 1918 study patients (335 metformin nonusers and 1583 metformin users) developed cancer. The incidence per 1000 person-years was 21.8 in metformin nonusers and 13.2 in metformin users. Metformin users had a reduced risk of cancer, even after adjustment for demographic characteristics, metabolic parameters, diabetic complications, and other antidiabetic medications (hazard ratio 0.513, 95% confidence interval 0.318-0.826, P = .0060). Subgroup analysis of metformin users showed a reduced risk of cancer in males, patients < 65 years of age, patients with a T2DM duration < 5 years, nonobese patients, nonsmokers, and good glycemic control group.This large-scale, prospective, multicenter cohort study demonstrated an association between metformin use and reduced cancer risk in patients with T2DM.
流行病学文献表明，胰岛素抵抗、高胰岛素血症以及胰岛素样生长因子水平升高使2型糖尿病（T2DM）患者患癌风险更高。近期已对T2DM患者癌症发病率与抗糖尿病药物使用之间的关联进行了研究。关于二甲双胍与癌症风险之间的关联，报告结果相互矛盾。本研究的目的是调查韩国T2DM患者使用二甲双胍与癌症发病率之间的关系。来自韩国国家糖尿病项目（KNDP，2006 - 2014年）的数据被用于研究T2DM患者，该项目是韩国一项全国性、大规模、前瞻性、多中心队列研究。本研究纳入了年龄≥30岁且有完整病历的患者。排除了在KNDP登记时有任何癌症病史的患者，或在使用二甲双胍1年内被诊断患有任何类型癌症的患者。使用Kaplan - Meier方法绘制癌症发病率的生存曲线。在Cox比例风险回归分析中估计癌症的风险比和95%置信区间。在平均5.8年的随访期间，1918名研究患者（335名未使用二甲双胍者和1583名使用二甲双胍者）中有164人患癌。未使用二甲双胍者每1000人年的发病率为21.8，使用二甲双胍者为13.2。即使在对人口统计学特征、代谢参数、糖尿病并发症和其他抗糖尿病药物进行调整后，使用二甲双胍者患癌风险仍降低（风险比0.513，95%置信区间0.318 - 0.826，P = 0.0060）。对使用二甲双胍者的亚组分析显示，男性、年龄<65岁的患者、T2DM病程<5年的患者、非肥胖患者、不吸烟者以及血糖控制良好组患癌风险降低。这项大规模、前瞻性、多中心队列研究证明了T2DM患者使用二甲双胍与降低癌症风险之间存在关联。
