Metformin use and lung cancer survival: a population-based study in Norway

Br J Cancer. 2021 Mar;124(5):1018-1025. doi: 10.1038/s41416-020-01186-9. Epub 2020 Dec 2.

Abstract

Background: We assessed associations between metformin use and survival in a nationwide Norwegian cohort of lung cancer (LC) patients.

Methods: The study linked 22,324 LC patients from the Cancer Registry of Norway diagnosed 2005-2014 with the Norwegian Prescription Database. We estimated associations of pre- and post-diagnostic metformin use with overall survival (OS) and LC-specific survival (LCSS) using multivariable time-fixed and time-dependent Cox regression.

Results: Pre-diagnostic metformin use was not associated with improved survival in all patients. Nevertheless, pre-diagnostic metformin use was associated with better LCSS in squamous cell carcinoma (SCC) patients (hazard ratio (HR) = 0.79; 95% confidence interval (CI) 0.62-0.99) and in patients with regional stage SCC (HR = 0.67; 95%CI 0.47-0.95). Post-diagnostic metformin use was associated with improved LCSS in all patients (HR = 0.83; 95%CI 0.73-0.95), in patients with SCC (HR = 0.75; 95%CI 0.57-0.98), regional stage LC (HR = 0.74; 95%CI 0.59-0.94), and regional stage SCC (HR = 0.57; 95%CI 0.38-0.86). OS showed similar results. Analyses of cumulative use showed a dose-response relationship in all patients, patients with adenocarcinoma and SCC, and with regional and metastatic LC.

Conclusions: Metformin use was associated with improved survival, especially LCSS in patients with regional stage SCC. Further prospective studies are required to clarify the role of metformin in LC treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung / drug therapy
  • Adenocarcinoma of Lung / epidemiology
  • Adenocarcinoma of Lung / mortality*
  • Adenocarcinoma of Lung / pathology
  • Aged
  • Aged, 80 and over
  • Carcinoma, Large Cell / drug therapy
  • Carcinoma, Large Cell / epidemiology
  • Carcinoma, Large Cell / mortality*
  • Carcinoma, Large Cell / pathology
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / epidemiology
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / epidemiology
  • Carcinoma, Squamous Cell / mortality*
  • Carcinoma, Squamous Cell / pathology
  • Combined Modality Therapy
  • Female
  • Follow-Up Studies
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / epidemiology
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / pathology
  • Male
  • Metformin / therapeutic use*
  • Middle Aged
  • Norway / epidemiology
  • Prognosis
  • Small Cell Lung Carcinoma / drug therapy
  • Small Cell Lung Carcinoma / epidemiology
  • Small Cell Lung Carcinoma / mortality*
  • Small Cell Lung Carcinoma / pathology
  • Survival Rate

Substances

  • Hypoglycemic Agents
  • Metformin