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

Fu-Shun Yen,James Cheng-Chung Wei,Chih-Cheng Hsu,Weishan Chen,Chii-Min Hwu,Stelios Loukides

doi:10.1371/journal.pone.0204859

Abstract

BackgroundsFew 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.MethodsWe 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.ResultsA 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).ConclusionThis 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.

Highlights

Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory lung disease that blocks airflow [1]
A total of 19,505 metformin users were matched to 19,505 nonusers in the cohort of diabetes with stable COPD
We identified variables that might influence the risk of death: demographic characteristics; comorbidities diagnosed before the index date; and use of specific classes of drugs such as other oral antidiabetic drugs (OAD, including: sulfonylureas, meglitinides, α-glucosidase inhibitor, thiazolidinedione, dipeptidyl peptidase-4 inhibitors, and insulin), antihypertensive drugs, COPD drugs, statins, and aspirin

Summary

Introduction

Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory lung disease that blocks airflow [1]. 8%–22% of adults aged 40 years and older have COPD [2], and the estimated global prevalence is 11.7%. 400 million people around the world are affected by COPD [3]. 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 [4]. 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 [7]

Methods

Results

Conclusion