Metformin linked to fewer asthma attacks, greater impact with added GLP-1 agonist

Key takeaways:

• Receipt of metformin for type 2 diabetes in patients with asthma may also decrease negative outcomes related to asthma.
• Researchers found no modification to the relationship based on BMI and asthma severity.

Among adults with asthma and type 2 diabetes, there was a link between metformin use and fewer asthma attacks, according to results published in JAMA Internal Medicine.

Additionally, a link between add-on GLP-1 receptor agonists and even fewer asthma attacks was reported in this population, according to researchers.

“The effect was very strong, nearly 30% reduction with metformin alone (first line treatment for type 2 diabetes) but an additional 40% with GLP-1 receptor agonists (eg, Wegovy [semaglutide, Novo Nordisk]), and unexpectedly it was effective for all asthma patients, including those with higher or lower BMI, and with all different types of asthma,” Chloe I. Bloom, BSc, MSc, PhD, clinical senior lecturer in respiratory epidemiology at National Heart and Lung Institute, Imperial College London, told Healio.

In a cohort study, Bloom and colleagues analyzed adults with asthma and type 2 diabetes from the 2004 to 2020 U.K. Clinical Practice Research Datalink Aurum to uncover if metformin is linked to asthma attacks. The link between various add-on antidiabetic medications — GLP-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, sulphonylureas, sodium-glucose cotransporter-2 inhibitors and insulin — and asthma attacks was also investigated.

This analysis was divided into two cohorts. The self-controlled case series (SCCS) included 4,278 adults (mean age, 52.9 years; 61.2% women; 80.3% white; 70.8% with obesity), whereas the inverse probability of treatment weighting (IPTW) cohort included 8,424 adults (55.7% women) either exposed (n = 5,892; mean age, 59.7 years) or unexposed (n = 2,537; mean age, 61.6 years) to metformin.

In the SCCS cohort, researchers used fixed-effect conditional Poisson models and reported a significant link between metformin and fewer asthma attacks (adjusted incidence rate ratio [IRR] = 0.68; 95% CI, 0.62-0.75) based on the 12 months before vs. after exposure.

This relationship was also observed in the IPTW cohort via weighted Cox proportional hazards models showing a decreased risk for asthma attacks with metformin (HR = 0.76; 95% CI, 0.67-0.85), according to the study.

Notably, researchers discovered “no evidence of significant residual confounding” using negative control analyses.

“Metformin is so safe it is used in pregnancy,” Bloom told Healio. “[It is also] cheap for patients and health care systems and readily available. We should look for diabetes in asthma patients early and when we find it, treat it, as we may improve both their asthma and their diabetes.”

After finding the above link between metformin and fewer asthma attacks, researchers looked at whether hemoglobin A_1C levels, BMI, blood eosinophil cell counts and asthma severity modified the relationship. None of the factors altered the observed relationship.

During the assessment of antidiabetic medications added on to metformin, a link between add-on GLP-1 receptor agonists and fewer asthma attacks over 365 days emerged in the SCCS cohort (IRR = 0.6; 95% CI, 0.49-0.73), according to the study. This was not evaluated in the IPTW cohort.

“From our study of over 2 million asthma patients, we also found that a significant proportion of overweight and obese patients [71.2%] did not have their blood checked to see if they have diabetes, even though they have other risk factors alongside their elevated BMI, such as the use of steroids for their asthma,” Bloom told Healio.

“Furthermore, many patients with evidence of high glucose levels did not have their diabetes diagnosed or treated, yet metformin is cheap, easily available, safe and an oral tablet that may treat both their asthma and their diabetes,” Bloom added.

Moving forward, Bloom said metformin should be assessed under a different type of study.

“The future is a trial to investigate how effective metformin is under rigorous trial conditions, including in people without diabetes,” Bloom told Healio. “This could have a large impact globally as metformin is relatively cheap and is on the WHO essentials medicines list.”

For more information:

Chloe I. Bloom, BSc, MSc, PhD, can be reached at chloe.bloom06@imperial.ac.uk.