Metformin use and respiratory outcomes in asthma-COPD overlap

Tianshi David Wu,Nadia N Hansel,Nirupama Putcha,Ashraf Fawzy,Jessica Bon,Robert A Wise,Gregory L Kinney,Maniraj Neupane,Meredith C Mccormack,Vickram Tejwani

doi:10.1186/s12931-021-01658-3

Abstract

BackgroundMetformin is associated with improved respiratory outcomes in asthma; however, metformin in COPD and asthma-COPD overlap (ACO) remains unexplored.ObjectiveTo determine the association between metformin use and respiratory outcomes in COPD and ACO.Study design and methodsParticipants with COPD (FEV1/FVC < 0.70) in the Genetic Epidemiology of COPD study (COPDGene®) were categorized as ACO (n = 510), defined as concurrent physician-diagnosed asthma before age 40 years, or COPD alone (n = 3459). We estimated the association of baseline metformin use with (1) rate of total and severe respiratory exacerbations during follow-up, (2) cross-sectional St. George’s Respiratory Questionnaire (SGRQ) score, six-minute walk distance (6MWD), and post-bronchodilator FEV1 percent predicted (FEV1pp), and (3) 5-year change in SGRQ, 6MWD, and FEV1pp. We also examined change in SGRQ, 6MWD and FEV1pp among participants who initiated metformin during follow-up (n = 108) compared to persistent metformin non-users (n = 2080). Analyses were adjusted for sociodemographic factors, medications, and comorbidities.ResultsAmong participants with ACO, metformin use was associated with lower rate of total (adjusted incidence rate ratio [aIRR] 0.3; 95% confidence interval [95%CI] 0.11, 0.77) and severe exacerbations (aIRR 0.29; 95%CI 0.10, 0.89). Among participants with COPD alone, there was no association between metformin use with total (aIRR 0.98; 95%CI 0.62, 1.5) or severe exacerbations (aIRR 1.3; 95% CI 0.68, 2.4) (p-interaction < 0.05). Metformin use was associated with lower baseline SGRQ score (adjusted mean difference [aMD] − 2.7; 95%CI − 5.3, − 0.2) overall. Metformin initiation was associated with improved SGRQ score (aMD –10.0; 95% CI − 18.7, − 1.2) among participants with ACO but not COPD alone (p-interaction < 0.05). There was no association between metformin use and 6MWD or FEV1pp in any comparison.ConclusionsMetformin use was associated with fewer respiratory exacerbations and improved quality of life among individuals with ACO but not COPD alone. Results suggest a potential role for metformin in ACO which requires further prospective study.Trial Registry: NCT00608764

Highlights

Metformin is associated with improved respiratory outcomes in asthma; metformin in Chronic obstructive pulmonary disease (COPD) and asthma-COPD overlap (ACO) remains unexplored
Among participants with ACO, metformin use was associated with lower rate of total and severe exacerbations
Among participants with COPD alone, there was no association between metformin use with total or severe exacerbations (p-interaction < 0.05)

Summary

Introduction

Metformin is associated with improved respiratory outcomes in asthma; metformin in COPD and asthma-COPD overlap (ACO) remains unexplored. Individuals with asthma-COPD overlap (ACO) share clinical and physiologic features of both asthma and COPD [1]. Because medication trials for asthma and COPD have generally excluded individuals with the opposing condition, evidence-based treatments for ACO remain sparse [4]. A study of Taiwan’s National Health Insurance Program reported a higher risk of pneumonia and hospitalization for COPD among metformin users [8].

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