title: Association between metformin use and mortality in patients with type 2 diabetes mellitus and localized resectable pancreatic cancer: a nationwide population-based study in korea.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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).
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea.
authors.forename: Won Il
authors.initials: WI
authors.lastname: Jang
authors.affiliation: 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.
authors.forename: Mi-Sook
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Division for Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul 04554, Republic of Korea.
authors.forename: Shin Hee
authors.initials: SH
authors.lastname: Kang
authors.affiliation: Division for Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul 04554, Republic of Korea.
authors.forename: Ae Jung
authors.initials: AJ
authors.lastname: Jo
authors.affiliation: Division for Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul 04554, Republic of Korea.
authors.forename: Yun Jung
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Division for Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul 04554, Republic of Korea.
authors.forename: Ha Jin
authors.initials: HJ
authors.lastname: Tchoe
authors.affiliation: Division for Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul 04554, Republic of Korea.
authors.forename: Chan Mi
authors.initials: CM
authors.lastname: Park
authors.affiliation: Division for Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul 04554, Republic of Korea.
authors.forename: Hyo Jeong
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Division for Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul 04554, Republic of Korea.
authors.forename: Jin A
authors.initials: JA
authors.lastname: Choi
authors.affiliation: Department of Anatomy, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
authors.forename: Hyung Jin
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea.
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Paik
authors.affiliation: Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea.
authors.forename: Young Seok
authors.initials: YS
authors.lastname: Seo
authors.affiliation: Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea.
authors.forename: Hyung Jun
authors.initials: HJ
authors.lastname: Yoo
authors.affiliation: Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea.
authors.forename: Jin-Kyu
authors.initials: JK
authors.lastname: Kang
authors.affiliation: Department of Internal Medicine, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea.
authors.forename: Chul Ju
authors.initials: CJ
authors.lastname: Han
authors.affiliation: Department of Internal Medicine, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea.
authors.forename: Yeon Ju
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Surgery, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea.
authors.forename: Sang Beom
authors.initials: SB
authors.lastname: Kim
authors.affiliation: Division for Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul 04554, Republic of Korea.
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Ko
mesh_terms: D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D015999:Multivariate Analysis; D010180:Pancreatectomy / Q000009:adverse effects / Q000401:mortality*; D016577:Pancreaticoduodenectomy / Q000009:adverse effects / Q000401:mortality*; D011471:Prostatic Neoplasms / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D065840:Protective Factors; D012042:Registries; D056910:Republic of Korea; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin
keywords: diabetes; metformin; nationwide database; pancreatic cancer; resection