Increased BMI and type 2 diabetes are more prevalent among patients with asthma and contribute to a higher incidence rate of asthma attacks. Experimental studies show that the diabetes treatment metformin and glucagon-like peptide-1 receptor agonists (GLP-1RA) reduce airway inflammation, hyperresponsiveness, and remodeling. Nevertheless, epidemiological data are still lacking.
A study published in JAMA Network, evaluated that in patients with asthma and diabetes, are metformin (a first-line diabetes medication) or any add-on antidiabetic medications associated with a reduced risk of asthma attacks? To address this issue, the researchers performed a self-controlled case series and a population-based cohort study of 12702 asthma patients which revealed that metformin use was associated with morbidity due to asthma exacerbation by 30% and glucagon-like peptide-1 receptor agonists contributed an additional lowering of 40% obesity-related attacks. Associations were identified irrespective of glycemic control, weight, or asthma phenotype.
To evaluate an association of metformin and add-on antidiabetic medications (GLP-1RA, DPP-4 inhibitors, sulfonylureas, SGLT-2 inhibitors, and insulin) with asthma attacks. The analysis leveraged data from the UK Clinical Practice Research Datalink (CPRD)-Uranus edition linked Hospital admission and mortality data from 2004 to 2020. A triangulation approach was used that enhanced robustness by applying two distinct approaches: a self-controlled case series (SCCS) and a metformin new user cohort with inverse probability of treatment weighting (IPTW). Included participants were only adults aged 35 to 74 years without a history of diabetes and were in metformin treatment. To understand how different metabolic phenotypes (e.g. BMI, glycemic control) affect different asthma phenotypes (e.g. type 2 inflammation, asthma severity) interaction analyses were performed. In order to determine the existence of bias negative-control analyses were performed.
Among more than two million adults with asthma, 4,278 patients (2,617 women [61.2%], mean age [SD], 52.9 [13.6] years) were selected for the SCCS and 8,424 patients (4,690 women [55.7%], unexposed: mean age [SD], 61.6 [13.2] years, exposed: mean age [SD], 59.7 [13.7] years) were selected for the IPTW cohort. It was demonstrated that the asthma attacks of like degree were fewer for this group than for all other groups with the same magnitude of metformin treatment in both cases (SCCS: IRR, 0.68; 95% CI, 0.62-0.75; IPTW: HR, 0.76; 95% CI, 0.67-0.85). The negative control analyses showed no sign of considerable distorting bias. No effect modification was found in terms of diabetes patients’ hemoglobin hemoglobin A1C (HbA1c) levels, BMI, blood eosinophil cell counts, or asthma severity. The only add-on antidiabetic medication to exhibit helpful interaction was GLP-1RA (SCCS: IRR, 0.60; 95% CI, 0.49-0.73).
Metformin was the primary exposure while the add-on antidiabetic drugs were secondary exposures. The most important objective was the occurrence of the first asthma exacerbation (short period of use of oral corticosteroids, unplanned admission to the hospital for any asthma-related issue, or death) within the invitational period of 12 months. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were computed using fixed-effect Conditional Poisson models for the SCCS, while hazard ratios (HRs) for the cohort were obtained using weighted Cox proportional hazards models.
The results of this cohort study suggest that metformin was associated with a lower rate of asthma attacks, with further reductions with the use of GLP-1RA. This appeared to be associated with mechanisms other than through glycemic control or weight loss and occurred across asthma phenotypes.
Reference: Lee B, Man KKC, Wong E, Tan T, Sheikh A, Bloom CI. Antidiabetic Medication and Asthma Attacks. JAMA Intern Med. Published online November 18, 2024. doi: 10.1001/jamainternmed.2024.5982
