Metformin exposure is associated with improved progression-free survival in diabetic patients after resection for early-stage non-small cell lung cancer

J Thorac Cardiovasc Surg. 2016 Jul;152(1):55-61.e1. doi: 10.1016/j.jtcvs.2016.03.094. Epub 2016 Apr 14.


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.

Keywords: Metformin; diabetes; lung cancer; outcomes; survival.

MeSH terms

  • Aged
  • Carcinoma, Non-Small-Cell Lung / complications
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / surgery*
  • Diabetes Mellitus
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Disease-Free Survival
  • Female
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Lung Neoplasms / complications
  • Lung Neoplasms / pathology
  • Lung Neoplasms / surgery*
  • Male
  • Metformin / therapeutic use*
  • Neoplasm Recurrence, Local / prevention & control*
  • Neoplasm Staging
  • Proportional Hazards Models


  • Hypoglycemic Agents
  • Metformin