Tianshi David Wu1,2,3, Ashraf Fawzy3, Gregory L Kinney4, Jessica Bon5,6, Maniraj Neupane7, Vickram Tejwani3, Nadia N Hansel3, Robert A Wise3, Nirupama Putcha3, Meredith C McCormack8. 1. Section of Pulmonary, Critical Care, and Sleep Medicine, Baylor College of Medicine, Houston, TX, USA. 2. Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey VA Medical Center, Houston, TX, USA. 3. Division of Pulmonary and Critical Care Medicine, Johns Hopkins School of Medicine, 1830 E. Monument St. 5th Floor, Baltimore, MD, 21205, USA. 4. Department of Epidemiology, Colorado School of Public Health, Aurora, CO, USA. 5. Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA. 6. VA Pittsburgh Healthcare System, Pittsburgh, PA, USA. 7. Department of Critical Care Medicine, National Institutes of Health, Bethesda, MD, USA. 8. Division of Pulmonary and Critical Care Medicine, Johns Hopkins School of Medicine, 1830 E. Monument St. 5th Floor, Baltimore, MD, 21205, USA. mmccor16@jhmi.edu.
Abstract
BACKGROUND: Metformin is associated with improved respiratory outcomes in asthma; however, metformin in COPD and asthma-COPD overlap (ACO) remains unexplored. OBJECTIVE: To determine the association between metformin use and respiratory outcomes in COPD and ACO. STUDY DESIGN AND METHODS: Participants 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. RESULTS: Among 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. CONCLUSIONS: Metformin 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.
BACKGROUND:Metformin is associated with improved respiratory outcomes in asthma; however, metformin in COPD and asthma-COPD overlap (ACO) remains unexplored. OBJECTIVE: To determine the association between metformin use and respiratory outcomes in COPD and ACO. STUDY DESIGN AND METHODS: Participants 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. RESULTS: Among 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. CONCLUSIONS:Metformin 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.
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