medwireNews: The diabetes drug metformin significantly reduces the number of exacerbations experienced by people with asthma, and the effect is greater still in those also taking add-on antidiabetic glucagon-like peptide (GLP)-1 receptor agonists, show UK study results.
During 12 months of follow-up, metformin use reduced the risk for asthma exacerbation by 32% versus no metformin in a self-controlled case series (SCCS) and by 24% in a metformin new-user population-based cohort using inverse probability of treatment weighting (IPTW), report the researchers who combined the two research approaches to increase robustness.
“[T]he study findings suggest dual benefit, potential for repurposing metformin to reduce asthma attacks, and a benefit of early pharmacological intervention for adults with asthma and metabolic dysfunction,” remark Chloe Bloom, from Imperial College London, UK, and colleagues in JAMA Internal Medicine.
The team examined the association between metformin and incidence of asthma exacerbations, defined as needing a short course of oral corticosteroids [5–7 days], an asthma-related emergency department visit, hospital admission or death, in 12,702 adults with asthma and type 2 diabetes. The patients had not previously been prescribed metformin and were included in the UK Clinical Practice Research Datalink Aurum between 2004 and 2020.
Participants in the SCCS cohort (n=4278, 61% women) acted as their own control, with 12 months’ observation both before and after exposure to metformin. For the IPTW cohort (n=8424, 55% women), follow-up began on the date of first metformin prescription for those exposed (n=5892) and date of cohort entry for those not exposed (n=2537).
Metformin was associated with a significant incidence rate ratio (IRR) of 0.68 for asthma exacerbation in the SCCS cohort, after adjusting for age, report Bloom and colleagues, with the reduction occurring within 3 months of follow-up (IRR=0.66) and continuing for 9 months (IRR=0.70). The number needed to treat with 1 year of metformin to prevent one asthma attack was 14, the team estimates.
Similarly, metformin was associated with a significant hazard ratio of 0.76 for an asthma exacerbation during follow-up in the IPTW cohort.
Of the add-on antidiabetic drugs taken by patients, only GLP-1 receptor agonsists caused a significant, persistent additional decrease in asthma exacerbation, with IRRs of 0.60 over the course of 1 year of treatment, 0.45 in the first 3 months of treatment, 0.62 in the 3–6 months of treatment and 0.66 in months 6–12 of treatment.
While GLP-1 receptor agonist treatment “shows potential,” metformin has “considerable advantages, including global availability and affordability,” remark Bloom et al.
They note that considering participants’ glycated hemoglobin, baseline BMI, asthma phenotype, and sex “did not modify the association between metformin and asthma attacks,” implying that “metformin’s mechanism of action in reducing asthma attacks was not associated with its antiglycemic or weight loss actions.”
The team concludes: “These findings suggest potential for repurposing antidiabetic drugs to much-needed alternative treatments for asthma.”
In an accompanying comment, Katherine Cahill (Vanderbilt University Medical Centre, Nashville, Tennessee, USA) and Dinah Foer (Brigham and Women’s Hospital, Boston, Massachusetts, USA) suggest that the study by Bloom et al encourages recognition of “asthma as a relevant type 2 diabetes comorbidity,” adding that there is a need to “reach across specialties to improve care for this vulnerable population.”
The pair concludes: “Reducing asthma exacerbation risk, and subsequently systemic corticosteroid exposure is a boon to patients and clinicians as they work in parallel to address glycemic control and weight management.”
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JAMA Intern Med 2024; doi:10.1001/jamainternmed.2024.5982
JAMA Intern Med 2024; doi:10.1001/jamainternmed.2024.5983
