Jang Won Il, Kim Mi-Sook, Kang Shin Hee, Jo Ae Jung, Kim Yun Jung, Tchoe Ha Jin, Park Chan Mi, Kim Hyo Jeong, Choi Jin A, Choi Hyung Jin, Paik Eun-Kyung, Seo Young Seok, Yoo Hyung Jun, Kang Jin-Kyu, Han Chul Ju, Kim Yeon Ju, Kim Sang Beom, Ko Min Jung
Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea.
Division for Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul 04554, Republic of Korea.
Oncotarget. 2017 Feb 7;8(6):9587-9596. doi: 10.18632/oncotarget.14525.
Preclinical studies support an antitumor effect of metformin. However, clinical studies have conflicting results and metformin's effect remains controversial. The aim of this study was to evaluate metformin's effect on clinical outcomes in diabetic patients with pancreatic cancer treated with curative resection.
A total of 764 patients underwent curative resection, met none of the exclusion criteria, and were prescribed oral hypoglycemic agents. The cancer-specific survival (5-year, 31.9% vs. 22.2%, p < 0.001) was significantly higher in the 530 metformin users than in the 234 diabetic metformin non-users. After multivariable adjustments, metformin users had significantly lower cancer-specific mortality as compared with metformin non-users (hazard ratio, 0.727; 95% confidence interval, 0.611-0.868). Cubic spline regression analysis demonstrated significantly decreased cancer-specific mortality with increasing dose of metformin (p = 0.0047).
Data were provided from the Korea Central Cancer Registry and the National Health Insurance Service in the Republic of Korea. The study cohort consisted of 28,862 patients newly diagnosed with pancreatic cancer between 2005 and 2011. Metformin exposure was determined from prescription information from 6 months before the first diagnosis of pancreatic cancer to last follow-up. The main outcome was cancer-specific survival.
This large study indicates that metformin might decrease cancer-specific mortality rates in localized resectable pancreatic cancer patients with pre-existing diabetes, independently of other factors, with a dose-response relationship.
临床前研究支持二甲双胍的抗肿瘤作用。然而，临床研究结果相互矛盾，二甲双胍的作用仍存在争议。本研究的目的是评估二甲双胍对接受根治性切除的糖尿病胰腺癌患者临床结局的影响。
共有764例患者接受了根治性切除，无一例符合排除标准，并被开具了口服降糖药。530名使用二甲双胍的患者的癌症特异性生存率（5年，31.9%对22.2%，p<0.001）显著高于234名未使用二甲双胍的糖尿病患者。经过多变量调整后，与未使用二甲双胍的患者相比，使用二甲双胍的患者癌症特异性死亡率显著降低（风险比，0.727；95%置信区间，0.611-0.868）。三次样条回归分析表明，随着二甲双胍剂量的增加，癌症特异性死亡率显著降低（p=0.0047）。
数据来自韩国中央癌症登记处和大韩民国国民健康保险服务中心。研究队列包括2005年至2011年间新诊断为胰腺癌的28862例患者。根据首次诊断胰腺癌前6个月至最后一次随访的处方信息确定二甲双胍暴露情况。主要结局是癌症特异性生存。
这项大型研究表明，二甲双胍可能会降低已患糖尿病的局限性可切除胰腺癌患者的癌症特异性死亡率，独立于其他因素，且存在剂量反应关系。
