Research shows how common diabetes medications are transforming asthma care by reducing attack rates, independent of weight or glycemic control.
Antidiabetic Medication and Asthma Attacks. Image Credit: Jelena Stanojkovic / Shutterstock
In a recent cohort study published in JAMA Internal Medicine, researchers in England investigated the effects of metformin and other medications for type 2 diabetes (T2D) on asthma attacks. They found that metformin was associated with a 30% reduction in asthma attacks, and glucagon-like peptide-1 receptor agonists (GLP-1RA) provided an additional 40% reduction, independent of weight, glycemic control, or asthma phenotype.
Background
Asthma, obesity, and T2D are closely linked, with T2D and related conditions increasing asthma attack risks and reliance on corticosteroids, which can worsen metabolic health. Metformin, the first-line treatment for T2D, is known for its safety and affordability and has potential anti-inflammatory and protective effects on the lungs. Its mechanisms may involve activation of adenosine monophosphate-activated protein kinase, repression of fatty acid-binding protein-4 pathways, and downregulation of insulin-like growth factor 1, all of which reduce airway inflammation and remodeling.
Previous studies suggested that metformin reduces asthma attacks, though some lacked control for factors like smoking and glycemic status. Additionally, GLP-1RAs show promise due to their lung-specific effects, reducing bronchial hyperresponsiveness and asthma attacks. However, their combined impact with metformin or across asthma phenotypes remains underexplored. Therefore, researchers in the present study examined the link between metformin and asthma attacks, considering metabolic and asthma phenotypes, and assessed the synergistic effects of add-on antidiabetic medications.
About the Study
Data were obtained from the United Kingdom Clinical Practice Research Datalink Aurum database, a nationally representative electronic healthcare dataset covering over two million adults. A total of 2,021,469 participants above 17 years of age and with asthma were included with at least two asthma codes within two years of entry. Patients with type 1 diabetes, chronic obstructive pulmonary disease, or chronic kidney disease were excluded. The metformin new user cohort consisted of individuals with T2D initiating metformin.
To ensure robust findings, a triangulation approach was employed: a self-controlled case series (SCCS) design (n=4,278), which controls for constant confounders like genetics and socioeconomic status, and an inverse probability of treatment weighting (IPTW) cohort (n=8,424), which addressed indication bias.
Metformin exposure was defined by regular prescriptions (every two months), excluding concurrent initiation with inhaled corticosteroids or use of other antidiabetic drugs. Dietary advice was used as a control exposure in the SCCS design.
The primary outcome was asthma attacks at 12-month follow-up, defined by oral corticosteroid use, emergency visits, hospitalizations, or death. Covariates included age, sex, body mass index (BMI), glycemic control, asthma severity, and smoking history.
Statistical methods included Poisson and weighted Cox models, as well as stratified and sensitivity analyses. The study also evaluated add-on antidiabetic drugs, such as GLP-1 receptor agonists, and controlled for negative outcomes like unrelated hospitalizations to mitigate bias.
Results and Discussion
A total of 81.5% of participants had a recorded BMI. Among them, 53.9% were overweight or obese, and 6.9% had T2D, with obesity significantly contributing to T2D prevalence. Glycemic assessment was low, with 71.2% of patients with overweight or obesity lacking glycated hemoglobin (HbA1c) or glucose measurements.
In the SCCS analysis, metformin was associated with a significant reduction in asthma attacks (P < .001). This effect appeared within three months and persisted for a year. In the IPTW cohort, metformin users showed a 24% lower risk of asthma attacks (weighted hazard ratio 0.76).
Sensitivity analysis confirmed the main results. Kaplan-Meier and weighted cumulative incidence plots also highlighted a lower incidence of asthma attacks in metformin users.
In the negative control analyses, no associations were found between metformin and unrelated outcomes like hospital admissions for abdominal pain or minor ailments, supporting the specificity of the findings. Among add-on antidiabetic drugs, only GLP-1 receptor agonists (GLP-1RA) showed a further and sustained reduction in asthma attacks (IRR 0.60).
The effect of metformin on asthma attacks was not modified by BMI, HbA1c, eosinophil count, asthma severity, or sex. Changes in HbA1c levels were not found to influence the association.
These findings suggest that metformin, alone or with GLP-1RA, may reduce asthma attacks regardless of metabolic or asthma phenotypes. The study is strengthened by using a large, robust healthcare database, employing triangulation methods for reproducibility, and mitigating confounding through SCCS design, new user cohort analysis, and negative control analyses. However, the study is limited by residual confounding, lack of medication adherence and dose data, inability to assess weight changes, and absence of information on asthma biologics.
Conclusion
In conclusion, the study suggests that metformin may reduce asthma attacks by 30%, with an additional 40% reduction when combined with GLP-1RA. This highlights the potential to repurpose antidiabetic drugs for asthma treatment. Further research and clinical trials are needed to confirm these effects and understand the underlying mechanisms.
