Effects of metformin use on total mortality in patients with type 2 diabetes and chronic obstructive pulmonary disease: A matched-subject design

PLoS One. 2018 Oct 4;13(10):e0204859. doi: 10.1371/journal.pone.0204859. eCollection 2018.

Abstract

Backgrounds: Few studies have investigated the therapeutic effects of metformin in patients with type 2 diabetes mellitus (T2DM) and chronic obstructive pulmonary disease (COPD). We compared the risk of all-cause mortality between metformin users and nonusers.

Methods: We conducted a retrospective cohort study for patients with T2DM and COPD who were enrolled between January 1, 2000 and June 30, 2012. Individuals with exacerbated symptoms who were hospitalized or sent to the emergency department (ED) were identified as having exacerbated COPD; outpatient claims were identified as having stable COPD. A total of 40,597 metformin users and 39,529 nonusers comprised the cohort of stable COPD; 14,001 metformin users and 21,613 nonusers comprised the cohort of exacerbated COPD. Users and nonusers were matched using propensity score (1:1). Our primary outcome was all-cause mortality.

Results: A total of 19,505 metformin users were matched to 19,505 nonusers in the cohort of diabetes with stable COPD. The mean follow-up time was 3.91 years. All-cause mortality was reported in 1326 and 1609 metformin users and nonusers, respectively. After multivariate adjustment, metformin users had lower risk of mortality (adjusted hazard ratio [aHR] = 0.84, p < 0.0001). Metformin users had significantly lower risk of noncardiovascular death (aHR = 0.86, p = 0.0008). A total of 7721 metformin users were matched to 7721 nonusers in the cohort of diabetes with exacerbated COPD. The mean follow-up time was 3.18 years. All-cause mortality was reported in 1567 and 1865 metformin users and nonusers, respectively. After multivariate adjustment, metformin users had significantly lower risk of mortality (aHR = 0.89, p = 0.002) and cardiovascular death (aHR = 0.70, p = 0.01).

Conclusion: This large-series, nationwide cohort study demonstrated that metformin use could significantly lower the risk of all-cause mortality in patients with T2DM and either stable or exacerbated COPD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cause of Death
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / mortality
  • Emergency Medical Services / statistics & numerical data
  • Female
  • Hospitalization / statistics & numerical data
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Metformin / administration & dosage*
  • Metformin / therapeutic use
  • Middle Aged
  • Propensity Score
  • Pulmonary Disease, Chronic Obstructive / mortality*
  • Retrospective Studies

Substances

  • Hypoglycemic Agents
  • Metformin

Grants and funding

This work was supported by grants from the Ministry of Health and Welfare, Taiwan (MOHW107-TDU-B-212-123004), China Medical University Hospital, Academia Sinica Stroke Biosignature Project (BM10701010021), MOST Clinical Trial Consortium for Stroke (MOST 106-2321-B-039-005).”, Tseng-Lien Lin Foundation, Taichung, Taiwan, and Katsuzo and Kiyo Aoshima Memorial Funds, Japan. Foundation, Taichung, Taiwan, and Katsuzo and Kiyo Aoshima Memorial Funds, Japan (WC received the funding). The funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding authors had full access to all data in the study and had final responsibility for the decision to submit for publication.