title: Cumulative Metformin Use and Its Impact on Survival in Gastric Cancer Patients After Gastrectomy.
abstract: OBJECTIVE
  The aim of this study was to evaluate the association between metformin and survival of gastric cancer (GC) patients.
  
  
  BACKGROUND
  Metformin has recently received attention as a potential anticancer treatment. However, no study has shown the survival benefit of metformin for GC patients.
  
  
  METHODS
  A total of 1974 GC patients who underwent curative gastrectomy were compared for survival according to groups; 132 diabetic patients treated with metformin, 194 diabetic patients without metformin, and 1648 non-diabetic patients.
  
  
  RESULTS
  During the median follow-up period of 6.2 years (interquartile range, 4.7-7.8 years), 381 patients (19.3%) died, including 302 (15.3%) who died from GC. The non-diabetic patients had significantly better recurrence-free survival (RFS; P < 0.0001), cancer-specific survival (CSS; P = 0.006), and overall survival (OS; P < 0.0001). However, the diabetic patients treated with metformin had a significantly better prognosis than those who were not (OS: hazard ratio [HR] = 0.584, 95% confidence interval [CI], 0.369-0.926; CSS: HR = 0.57, 95% CI, 0.334-0.975; RFS: HR = 0.633, 95% CI, 0.410-0.977), and metformin treatment prolonged survival in diabetic patients to a rate comparable to that in non-diabetic patients. In multivariable analysis using the Cox proportional hazard model with time-dependent covariates, each cumulative 6 months of metformin use was significantly associated with a decreased risk of recurrence, cancer-specific mortality, and all-cause mortality (RFS: HR = 0.864, 95% CI, 0.797-0.937; CSS: HR = 0.865, 95% CI, 0.782-0.958; OS: HR 0.870, 95% CI, 0.801-0.945).
  
  
  CONCLUSIONS
  The increased cumulative duration of metformin use decreased the recurrence, all-cause mortality, and cancer-specific mortality rates among GC patients with diabetes who underwent gastrectomy.
authors.affiliation: *Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea †Department of Biostatistics, Yonsei University College of Medicine, Seoul, Republic of Korea ‡Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea §Department of Surgery, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Choong-kun
authors.initials: CK
authors.lastname: Lee
authors.forename: Minkyu
authors.initials: M
authors.lastname: Jung
authors.forename: Inkyung
authors.initials: I
authors.lastname: Jung
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Heo
authors.forename: Yong Hyu
authors.initials: YH
authors.lastname: Jeong
authors.forename: Ji Yeong
authors.initials: JY
authors.lastname: An
authors.forename: Hyoung-Il
authors.initials: HI
authors.lastname: Kim
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Cheong
authors.forename: Woo Jin
authors.initials: WJ
authors.lastname: Hyung
authors.forename: Sung Hoon
authors.initials: SH
authors.lastname: Noh
authors.forename: Hyo Song
authors.initials: HS
authors.lastname: Kim
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Rha
authors.forename: Hyun Cheol
authors.initials: HC
authors.lastname: Chung
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D048909:Diabetes Complications / Q000150:complications / Q000188:drug therapy*; D005260:Female; D005743:Gastrectomy; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000150:complications / Q000401:mortality* / Q000601:surgery*; D015996:Survival Rate; D055815:Young Adult
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin