TY - JOUR
T1 - Metformin use and respiratory outcomes in asthma-COPD overlap
AU - Wu, Tianshi David
AU - Fawzy, Ashraf
AU - Kinney, Gregory L.
AU - Bon, Jessica
AU - Neupane, Maniraj
AU - Tejwani, Vickram
AU - Hansel, Nadia N.
AU - Wise, Robert A.
AU - Putcha, Nirupama
AU - McCormack, Meredith C.
N1 - Funding Information:
COPDGene is supported by the National Heart, Lung, and Blood Institute (U01HL89897 and U01HL089856) and by the COPD Foundation through contributions made to an Industry Advisory Board comprised of AstraZeneca, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Novartis, Pfizer, Siemens, and Sunovion. TDW is supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Center for Innovations in Quality, Effectiveness and Safety (CIN 13-413). VT is supported by the National Heart, Lung, and Blood Institute (F32HL149258). MCM is supported by the National Institute of Environmental Health Sciences (P50ES018176), National Institute on Minority Health and Health Disparities (P50MD010431), and the United States Environmental Protection Agency (83615201 and 83615001). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, the Department of Veterans Affairs, the Environmental Protection Agency, or the United States government.
Funding Information:
NNH reports grants from the COPD Foundation, grants and personal fees from AstraZeneca and GlaxoSmithKline, grants from Boehringer Ingelheim, and personal fees from Mylan, unrelated to the submitted work. MCM reports royalties from UpToDate and personal fees from Aridis, GlaxoSmithKline, and Celgene, unrelated to the submitted work. RAW reports personal fees from AstraZeneca, Contrafect, Roche-Genentech, Merck, Verona, Mylan, Theravance, AbbVie, GSK, ChemRx, Kiniksa, Bristol Myers Squibb, Galderma, Kamada, Pulmonx, Kinevant, PureTech, Arrowhead, VaxArt, and Polarean, unrelated to the submitted work. TDW, AF, GLK, JB, MN, VT, and NP report no competing interests.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
KW - Asthma-COPD overlap
KW - Exacerbations
KW - Metformin
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U2 - 10.1186/s12931-021-01658-3
DO - 10.1186/s12931-021-01658-3
M3 - Article
C2 - 33637087
AN - SCOPUS:85101765243
SN - 1465-9921
VL - 22
JO - Respiratory research
JF - Respiratory research
IS - 1
M1 - 70
ER -