Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Liver Int. 2018 Nov;38(11):2018-2027. doi: 10.1111/liv.13872. Epub 2018 Jun 29.
Whether metformin may reduce hepatocellular carcinoma (HCC) risk requires confirmation.
Type 2 diabetes patients newly diagnosed during 1999-2005 and with 2 or more prescriptions of antidiabetic drugs were enrolled from the Taiwan's National Health Insurance database. A total of 173 917 ever-users and 21 900 never-users of metformin were identified (unmatched cohort). A 1:1 matched-pair cohort of 21 900 ever-users and 21 900 never-users based on a propensity score (PS) was created. Hazard ratios were estimated by Cox regression incorporated with the inverse probability of treatment weighting using the PS. In addition, interactions with aspirin and statin were evaluated.
In the unmatched cohort, 619 never-users and 2642 ever-users developed HCC, with a respective incidence of 668.0 and 330.7 per 100 000 person-years and an overall hazard ratio of 0.49 (95% confidence interval: 0.45-0.54). The hazard ratios for the first (<25.7 months), second (25.7-56.9 months) and third (>56.9 months) tertile of cumulative duration of metformin therapy were 0.89 (0.81-0.98), 0.50 (0.46-0.56) and 0.23 (0.21-0.26) respectively. Analyses of the matched cohort showed an overall hazard ratio of 0.76 (0.67-0.85), and the hazard ratios for the respective tertiles were 1.39 (1.19-1.62), 0.77 (0.65-0.91) and 0.37 (0.30-0.45). Aspirin and statin were observed to have a significant interaction with metformin.
Metformin was associated with a reduced risk of HCC in a dose-response pattern. Users of both metformin and aspirin or metformin and statin had the lowest risk.
二甲双胍是否可以降低肝细胞癌（HCC）的风险仍需要进一步证实。
本研究从台湾全民健康保险数据库中纳入了 1999 年至 2005 年期间新诊断为 2 型糖尿病且服用两种或以上降血糖药物的患者。共纳入 173917 例二甲双胍曾用者和 21900 例从未使用过二甲双胍的患者（未匹配队列）。根据倾向评分（PS），创建了 1：1 配对的二甲双胍曾用者和从未使用者队列（21900 例配对）。采用 Cox 回归模型，结合 PS 进行逆概率治疗加权，估计风险比（HR）。此外，还评估了与阿司匹林和他汀类药物的交互作用。
在未匹配队列中，619 例从未使用者和 2642 例曾使用者发生 HCC，相应的发病率为每 100000 人年 668.0 和 330.7，总体 HR 为 0.49（95%置信区间：0.45-0.54）。累积服用二甲双胍治疗时间的第一（<25.7 个月）、第二（25.7-56.9 个月）和第三（>56.9 个月）三分位的 HR 分别为 0.89（0.81-0.98）、0.50（0.46-0.56）和 0.23（0.21-0.26）。匹配队列分析显示总体 HR 为 0.76（0.67-0.85），相应三分位的 HR 分别为 1.39（1.19-1.62）、0.77（0.65-0.91）和 0.37（0.30-0.45）。观察到阿司匹林和他汀类药物与二甲双胍之间存在显著的交互作用。
二甲双胍的 HCC 发病风险呈剂量反应模式，与 HCC 风险降低相关。同时使用二甲双胍和阿司匹林或二甲双胍和他汀类药物的患者风险最低。
Zotero 插件