Metformin IN Asthma for overweight and obese individuals (MINA)

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PROJECT SUMMARY/ABSTRACT More than 40% of the 250 million people living with asthma in the United States are obese. Obese individuals with asthma are more likely to develop “obesity-associated asthma,” a phenotype that is exacerbation-prone and resistant to treatment. While weight loss is an effective treatment, this is difficult to attain and sustain, and consequently there are few effective and specific treatment options for this prevalent asthma phenotype. Obesity-induced metabolic inflammation, insulin resistance, and pre-diabetes may explain some of the excess morbidity of obesity-associated asthma. Metformin, the first-line treatment for type 2 diabetes, comprehensively treats these conditions. Preclinical data suggest that metformin improves airways hyperresponsiveness and allergic airway inflammation among animal models of obese asthma, and observational data have shown an inverse relationship between metformin use and risk of asthma exacerbation, suggesting that metformin may be beneficial among patients with asthma and elevated body mass index. The objective of this application is to conduct a pilot, six-month, randomized, placebo-controlled, parallel-arm, two-center trial of metformin among overweight and obese individuals with physician-diagnosed asthma recruited from Baylor College of Medicine and Johns Hopkins University. The pilot RCT will determine (1) feasibility of a study design that utilizes remote methods for research participation and (2) preliminary estimates of the effect of metformin on core patient- centered and physiologic outcomes. Completion of these aims will inform the decision to proceed with a pivotal multi-center efficacy RCT testing metformin among overweight and obese participants with asthma and inform specifics of its design and enrollment strategies. This project will provide findings that address an urgent research priority relevant to the millions of Americans with obesity-associated asthma.