Insulin resistance and asthma: from pathogenic pathways to therapeutic opportunities

Asthma is a chronic respiratory disease with a significant global burden. Several risk factors interact to contribute to the development of asthma. Large cross-sectional and longitudinal studies highlight a robust association between asthma and insulin resistance (IR) disorders such as metabolic syndrome, obesity, and T2DM, often leading to worse outcomes and higher morbidity.

To critically review current evidence linking IR and asthma, with emphasis on epidemiological associations, pathogenic mechanisms, and potential therapeutic implications, while identifying current knowledge gaps and translational challenges.

This narrative review was based on literature identified through PubMed, Scopus, and Google Scholar up to December 2025. Epidemiological, mechanistic, experimental, preclinical, and clinical studies relevant to the relationship between IR and asthma were evaluated, with particular attention to distinguishing preclinical findings from available clinical evidence.

Accumulating evidence from epidemiological studies demonstrates a robust association between asthma and IR-related disorders. IR and compensatory hyperinsulinemia may contribute to asthma through multiple interconnected mechanisms, including chronic low-grade inflammation, hormonal and endothelial dysfunction, oxidative stress, glucose intolerance, alterations in the gut microbiota, and shared genetic pathways. These mechanisms may promote airway inflammation, bronchial hyperresponsiveness, and asthma heterogeneity. Emerging preclinical and limited clinical evidence suggests that lifestyle interventions and selected pharmacological therapies targeting metabolic dysfunction may improve asthma-related outcomes. However, much of the current evidence remains observational or mechanistic, and randomized clinical trials specifically evaluating asthma outcomes are scarce.

IR may represent a common metabolic phenotype contributing to asthma heterogeneity and a potential therapeutic target. Nevertheless, the causal role of IR in asthma and the clinical utility of IR-targeted interventions remain incompletely established. Further prospective and interventional studies are needed to determine whether assessment and treatment of IR should be incorporated into routine asthma management.