title: Metformin exposure is associated with improved progression-free survival in diabetic patients after resection for early-stage non-small cell lung cancer.
abstract: OBJECTIVE
  There are little clinical data assessing the antineoplastic effect of metformin in patients with non-small cell lung cancer. We hypothesized that in diabetic patients undergoing pulmonary resection for early-stage non-small cell lung cancer, metformin exposure is associated with improved survival.
  
  
  METHODS
  An institutional database was used to identify patients with stage I or II non-small cell lung cancer who underwent pulmonary resection between 2004 and 2013. Patients were divided into 3 cohorts: type II diabetic patients with metformin exposure (cohort A, n = 81), type II diabetic patients without metformin exposure (cohort B, n = 57), and nondiabetic individuals (cohort C, n = 77). Univariate, multivariate, and propensity-matched analyses were performed to assess progression-free and overall survivals between groups.
  
  
  RESULTS
  A total of 215 patients with stage I and II non-small cell lung cancer treated with surgical resection were identified for analysis with a median follow-up of 19.5 months. Patients in cohort A had lower T- and N-stage tumors than those in cohorts B or C. However, on multivariate analysis adjusting for age, gender, and T and N stage, progression-free survival was greater for cohort A than cohort B (hazard ratio [HR], 0.410; 95% confidence interval, 0.199-0.874; P = .022) or cohort C (HR, 0.415; 95% confidence interval, 0.201-0.887; P = .017). Likewise, when propensity-matched analyses were performed, cohort A demonstrated a trend toward improved progression-free survival compared with cohort B (P = .057; HR, 0.44; c-statistic = 0.832) and improved progression-free survival compared with cohort C (P = .02; HR, 0.41; c-statistic = 0.843). No differences were observed in overall survival.
  
  
  CONCLUSIONS
  Metformin exposure in diabetic patients with early-stage non-small cell lung cancer may be associated with improved progression-free survival, but no effect was seen on overall survival. Further studies are warranted to evaluate if there is a therapeutic role for metformin in the treatment of non-small cell lung cancer.
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, Rush University Medical Center, Chicago, Ill.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Medairos
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, Rush University Medical Center, Chicago, Ill.
authors.forename: James
authors.initials: J
authors.lastname: Clark
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, Rush University Medical Center, Chicago, Ill.
authors.forename: Simon
authors.initials: S
authors.lastname: Holoubek
authors.affiliation: Department of General Surgery, Rush University Medical Center, Chicago, Ill.
authors.forename: John C
authors.initials: JC
authors.lastname: Kubasiak
authors.affiliation: Department of Biochemistry, Rush University Medical Center, Chicago, Ill.
authors.forename: Ravi
authors.initials: R
authors.lastname: Pithadia
authors.affiliation: Department of Pathology, Rush University Medical Center, Chicago, Ill.
authors.forename: Fatima
authors.initials: F
authors.lastname: Hamid
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, Rush University Medical Center, Chicago, Ill.
authors.forename: Gary W
authors.initials: GW
authors.lastname: Chmielewski
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, Rush University Medical Center, Chicago, Ill.
authors.forename: William H
authors.initials: WH
authors.lastname: Warren
authors.affiliation: Department of Preventative Medicine, Rush University Medical Center, Chicago, Ill.
authors.forename: Sanjib
authors.initials: S
authors.lastname: Basu
authors.affiliation: Department of Biochemistry, Rush University Medical Center, Chicago, Ill; Department of Pathology, Rush University Medical Center, Chicago, Ill.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Borgia
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, Rush University Medical Center, Chicago, Ill.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Liptay
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, Rush University Medical Center, Chicago, Ill. Electronic address: Christopher_W_Seder@rush.edu.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Seder
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000150:complications / Q000473:pathology / Q000601:surgery*; D003920:Diabetes Mellitus; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000150:complications / Q000473:pathology / Q000601:surgery*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D009367:Neoplasm Staging; D016016:Proportional Hazards Models
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin
keywords: Metformin; diabetes; lung cancer; outcomes; survival