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Comment
. 2025 Jan 1;185(1):16-25.
doi: 10.1001/jamainternmed.2024.5982.

Antidiabetic Medication and Asthma Attacks

Bohee Lee  1 , Kenneth K C Man  2 , Ernie Wong  1 , Tricia Tan  3 , Aziz Sheikh  4   5 , Chloe I Bloom  1
Affiliations
Comment

Antidiabetic Medication and Asthma Attacks

Bohee Lee et al. JAMA Intern Med. .

Abstract

Importance: Elevated body mass index (BMI) and type 2 diabetes are prevalent in asthma and are associated with an increase in the risk of asthma attacks. In experimental studies, the diabetes medications metformin and glucagon-like peptide-1 receptor agonists (GLP-1RA) have mitigated airway inflammation, hyperresponsiveness, and remodeling. However, epidemiological evidence is limited.

Objective: To estimate the association of metformin and add-on antidiabetic medications (GLP-1RA, dipeptidyl peptidase-4 inhibitors, sulphonylureas, sodium-glucose cotransporter-2 inhibitors, and insulin) with asthma attacks.

Design, setting, and participants: The study used data from the UK Clinical Practice Research Datalink (CPRD) Aurum linked hospital admissions and mortality data from 2004 to 2020. A triangulation approach was used that applied 2 distinct approaches to enhance robustness: a self-controlled case series (SCCS) and a metformin new user cohort with inverse probability of treatment weighting (IPTW). Eligible participants were new users of metformin with type 2 diabetes. To evaluate the association between metabolic phenotypes (BMI, glycemic control) and asthma phenotypes (type 2 inflammation, asthma severity), interaction analyses were conducted. Negative control analyses were conducted to assess for bias.

Exposure: The primary exposure was metformin; secondary exposures included add-on antidiabetic medications.

Main outcomes: The primary outcome was first asthma exacerbation (short course of oral corticosteroids, unscheduled asthma-related hospital attendance, or death) during 12-month follow-up. Incidence rate ratios (IRRs) with 95% CIs were estimated using fixed-effect conditional Poisson models in the SCCS, and hazard ratios (HRs) were estimated using weighted Cox proportional hazards models in the cohort.

Results: Of more than 2 million adults with asthma, 4278 patients (2617 women [61.2%]; mean [SD] age, 52.9 [13.6] years) were identified for the SCCS and 8424 patients (4690 women [55.7%]; unexposed: mean [SD] age, 61.6 [13.2] years; exposed: mean [SD] age, 59.7 [13.7] years) for the IPTW cohort. Metformin was found to be associated with fewer asthma attacks of similar magnitude in both approaches (SCCS: IRR, 0.68; 95% CI, 0.62-0.75; IPTW: HR, 0.76; 95% CI, 0.67-0.85). Negative control analyses did not find evidence of significant bias. Hemoglobin A1c levels, BMI, blood eosinophil cell counts, and asthma severity did not modify the association. The only add-on antidiabetic medication to have an additive association was GLP-1RA (SCCS: IRR, 0.60; 95% CI, 0.49-0.73).

Conclusions and relevance: 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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Lee reported grants from Asthma+Lung UK during the conduct of the study. Dr Man reported grants from the CW Maplethorpe Fellowship, European Commission Horizon 2020, National Institute for Health and Care Research (NIHR), UK, and Research Grant Council, Hong Kong outside the submitted work. Dr Wong reported personal fees from AstraZeneca and Chiesi, nonfinancial support from GSK, and grants from AstraZeneca outside the submitted work. Dr Sheikh reported grants from the Asthma UK Centre for Applied Research during the conduct of the study. Dr Bloom reported grants from Asthma + Lung UK during the conduct of the study as well as grants from NIHR outside the submitted work. No other disclosures were reported.

Comment on

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