Date Published: October 4, 2018
Publisher: Public Library of Science
Author(s): Fu-Shun Yen, Weishan Chen, James Cheng-Chung Wei, Chih-Cheng Hsu, Chii-Min Hwu, Stelios Loukides.
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.
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.
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). 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.
Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory lung disease that blocks airflow . Approximately 8%–22% of adults aged 40 years and older have COPD , and the estimated global prevalence is 11.7%. Approximately 400 million people around the world are affected by COPD . In 2015, COPD was the third leading cause of age-standardized mortality for both sexes, with approximately 3.2 million deaths caused by this disease . Because of inflammatory processes and the use of high-dose corticosteroids, COPD might increase the risk of developing type 2 diabetes mellitus (T2DM) [5, 6]. Among patients with COPD, 1.6%–16% had diabetes, and the prevalence increased as lung function deteriorated .
In total, 153,083 patients were newly diagnosed with T2DM and COPD; after excluding ineligible patients, 80,126 patients with T2DM and stable COPD and 35,614 patients with T2DM and exacerbated COPD in the LHDB between January 1, 2000 and December 31, 2012 comprised the overall cohorts of our study (Fig 1).
To our knowledge, this is the largest study comparing the long-term effects of metformin use and nonuse in patients with T2DM and COPD. We used 1:1 propensity score matching to compare all-cause mortality and metabolic acidosis between metformin users and nonusers in cohorts of 39,010 and 15,442 patients with T2DM and stable or exacerbated COPD, respectively. The results revealed that metformin use could significantly decrease the risk of all-cause mortality in patients with T2DM and stable and exacerbated COPD. This protective effect was consistent over subgroup analysis of gender, age, comorbidity, DCSI, and other antidiabetic drug use. In the cohort of patients with T2DM and stable COPD, the metformin users had significantly lower risk of non-CV death compared with the nonusers, whereas in the cohort of T2DM patients with exacerbated COPD, metformin users had significantly lower risk of CV death compared with the nonusers.
In this large nationwide, population-based cohort study, metformin use in patients with T2DM and COPD could lower the risk of all-cause mortality without increasing the risk of metabolic acidosis.