title: Association of Metformin Use With Cancer-Specific Mortality in Hepatocellular Carcinoma After Curative Resection: A Nationwide Population-Based Study.
abstract: Many preclinical reports and retrospective population studies have shown an anticancer effect of metformin in patients with several types of cancer and comorbid type 2 diabetes mellitus (T2DM). In this work, the anticancer effect of metformin was assessed in hepatocellular carcinoma (HCC) patients with T2DM who underwent curative resection.A population-based retrospective cohort design was used. Data were obtained from the National Health Insurance Service and Korea Center Cancer Registry in the Republic of Korea, identifying 5494 patients with newly diagnosed HCC who underwent curative resection between 2005 and 2011. Crude and adjusted hazard ratios (HRs) were calculated using Cox proportional hazard models to estimate effects. In the sensitivity analysis, we excluded patients who started metformin or other oral hypoglycemic agents (OHAs) after HCC diagnosis to control for immortal time bias.From the patient cohort, 751 diabetic patients who were prescribed an OHA were analyzed for HCC-specific mortality and retreatment upon recurrence, comparing 533 patients treated with metformin to 218 patients treated without metformin. In the fully adjusted analyses, metformin users showed a significantly lower risk of HCC-specific mortality (HR 0.38, 95% confidence interval [CI] 0.30-0.49) and retreatment events (HR 0.41, 95% CI 0.33-0.52) compared with metformin nonusers. Risks for HCC-specific mortality were consistently lower among metformin-using groups, excluding patients who started metformin or OHAs after diagnosis.In this large population-based cohort of patients with comorbid HCC and T2DM, treated with curative hepatic resection, metformin use was associated with improvement of HCC-specific mortality and reduced occurrence of retreatment events.
authors.affiliation: From the Department of Radiation Oncology (Y-SS, M-SK, WIJ), Korea Institute of Radiological and Medical Sciences; Division for Healthcare Technology Assessment Research (Y-JK, M-SK, SHK, HJT, CMP, AJJ, HJK, JAC, MJK), National Evidence-based Healthcare Collaborating Agency; Department of General Surgery (K-SS), Seoul National University Hospital; Department of General Surgery (SBK); Department of Internal Medicine (CJH, YJK), Korea Institute of Radiological and Medical Sciences; Department of Anatomy (HJC), Seoul National University College of Medicine, Seoul, Korea; and Department of Oncology (MNP), McGill University, Montreal, QC, Canada.
authors.forename: Young-Seok
authors.initials: YS
authors.lastname: Seo
authors.forename: Yun-Jung
authors.initials: YJ
authors.lastname: Kim
authors.forename: Mi-Sook
authors.initials: MS
authors.lastname: Kim
authors.forename: Kyung-Suk
authors.initials: KS
authors.lastname: Suh
authors.forename: Sang Bum
authors.initials: SB
authors.lastname: Kim
authors.forename: Chul Ju
authors.initials: CJ
authors.lastname: Han
authors.forename: Youn Joo
authors.initials: YJ
authors.lastname: Kim
authors.forename: Won Il
authors.initials: WI
authors.lastname: Jang
authors.forename: Shin Hee
authors.initials: SH
authors.lastname: Kang
authors.forename: Ha Jin
authors.initials: HJ
authors.lastname: Tchoe
authors.forename: Chan Mi
authors.initials: CM
authors.lastname: Park
authors.forename: Ae Jung
authors.initials: AJ
authors.lastname: Jo
authors.forename: Hyo Jeong
authors.initials: HJ
authors.lastname: Kim
authors.forename: Jin A
authors.initials: JA
authors.lastname: Choi
authors.forename: Hyung Jin
authors.initials: HJ
authors.lastname: Choi
authors.forename: Michael N
authors.initials: MN
authors.lastname: Polak
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Ko
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality*; D002423:Cause of Death; D015331:Cohort Studies; D015897:Comorbidity; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000401:mortality*; D018572:Disease-Free Survival; D005260:Female; D006306:Health Surveys; D006498:Hepatectomy; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D008687:Metformin / Q000009:adverse effects* / Q000627:therapeutic use*; D008875:Middle Aged; D056910:Republic of Korea; D012189:Retrospective Studies; D012306:Risk
chemical_list: D000970:Antineoplastic Agents; D008687:Metformin