The Role of Glucagon-Like Peptide-1 Receptor Agonists in Allergic Inflammation and Asthma: A Mechanistic Review.

Asthma and allergic diseases represent a substantial global health burden, frequently compounded by the modern epidemics of obesity and metabolic syndrome to create a complex immunometabolic challenge. The emerging epithelial barrier hypothesis provides a mechanistic framework linking environmental exposures to systemic inflammation and metabolic dysfunction. Standard therapies often fail to address these underlying systemic drivers, particularly in difficult-to-treat phenotypes like obesity-related asthma. This review explores the dual-action potential of glucagon-like peptide-1 receptor agonists (GLP-1RA) as a novel therapeutic strategy. Beyond their established roles in glycemic control and weight loss, GLP-1RA exert direct, weight-independent immunomodulatory effects. Mechanistic evidence demonstrates that the GLP-1 receptor (GLP-1R) is expressed on key immune cells, including eosinophils, macrophages, and Group 2 innate lymphoid cells. Agonism of these receptors suppresses Type 2 (T2) inflammation by reducing cytokine production (IL-5, IL-13) and upstream alarmins (IL-33). Furthermore, GLP-1R signalling enhances regulatory T cell function and may restore epithelial barrier integrity in both the gut and airways. Clinical observations suggest that GLP-1RA initiation improves asthma control and reduces exacerbations, often independently of body mass index reduction. However, prospective trials utilizing specific T2 biomarkers are needed to confirm these direct cellular mechanisms in humans. Transitioning to an immunometabolic approach with GLP-1RA may offer a comprehensive solution for patients at the intersection of metabolic and allergic disease.