Background: Patients with asthma frequently have comorbid obesity and type 2 diabetes (T2D), conditions associated with an increased risk of asthma attacks. Experimental studies suggest that metformin and glucagon-like peptide-1 receptor agonists (GLP-1RAs) can reduce airway inflammation and hyperresponsiveness. However, epidemiological evidence supporting these effects is limited.

Objective: To evaluate the association between metformin use, with or without add-on antidiabetic medications, and the risk of asthma attacks in patients with asthma and T2D.

Methods: This study utilized data from the UK Clinical Practice Research Datalink Aurum from 2004 to 2020, employing two analytical approaches: a self-controlled case series (SCCS) of 4,278 new metformin users with asthma who experienced asthma attacks, and a population-based cohort study using inverse probability of treatment weighting (IPTW) including 8,424 patients. The primary exposure was initiation of metformin; secondary exposures included add-on antidiabetic medications. The primary outcome was the first asthma exacerbation—defined as a short course of oral corticosteroids, unscheduled asthma-related hospital attendance, or death—during 12 months of follow-up.

Results: Metformin use was associated with a significant reduction in asthma attacks in both analyses. In the SCCS, metformin initiation was linked to a 32% reduction in risk (incidence rate ratio [IRR], 0.68; 95% CI, 0.62-0.75). In the IPTW cohort, metformin use was associated with a 24% reduction (hazard ratio [HR], 0.76; 95% CI, 0.67-0.85). Addition of GLP-1RAs led to a further reduction in asthma attacks (IRR, 0.60; 95% CI, 0.49-0.73). Associations were consistent regardless of glycemic control, body mass index, asthma severity, or blood eosinophil counts.

Conclusions: The findings suggest that metformin use is associated with a lower rate of asthma attacks among patients with asthma and T2D, with additional benefits when GLP-1RAs are added. These effects appear independent of glycemic control or weight loss and occur across different asthma phenotypes.

Implications for Practice: These results indicate potential for repurposing metformin as an adjunct therapy to reduce asthma attacks in patients with asthma and T2D. However, as observational studies cannot establish causality, clinicians should interpret these findings cautiously. The higher cost and side-effect profile of GLP-1RAs warrant careful consideration before widespread adoption.

Reference: Lee B, et al. Antidiabetic Medication and Asthma Attacks. JAMA Internal Medicine. 2024. DOI: http://doi.org/10.1001/jamainternmed.2024.5982