Metformin use and respiratory outcomes in asthma-COPD overlap

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

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.

Keywords: Asthma-COPD overlap; Exacerbations; Metformin.

Conflict of interest statement

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.

Figures

Fig. 1
Fig. 1
Incidence rate ratio (95% confidence interval) of metformin users compared to non-users stratified by presence of asthma diagnosed by a doctor before age 40. Models are adjusted for age, sex, race, education, post-bronchodilator FEV1 percent predicted, self-reported respiratory exacerbation in the prior 12 months (yes/no), smoking status, body mass index, inhaled corticosteroid use, oral corticosteroid use, other diabetes medication use, and comorbidity count. The p-value shown is for the interaction representing effect modification of Asthma-COPD overlap status on the association of metformin use with exacerbation rate

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