Asthma Exacerbations in Patients with Type 2 Diabetes and Asthma on Glucagon-like Peptide-1 Receptor Agonists

Abstract

Rationale: Glucagon-like peptide-1 receptor (GLP-1R) agonists are approved to treat type 2 diabetes mellitus and obesity. GLP-1R agonists reduce airway inflammation and hyperresponsiveness in preclinical models. Objectives: To compare rates of asthma exacerbations and symptoms between type 2 diabetic adults with asthma prescribed GLP-1R agonists and those prescribed sodium-glucose cotransporter-2 (SGLT-2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, sulfonylureas or basal insulin for diabetes treatment intensification. Methods: Electronic health records-based new-user, active comparator, retrospective cohort study of patients with type 2 diabetes and asthma newly prescribed GLP-1R agonists or comparator drugs, January 2000-March 2018. Primary outcome was asthma exacerbations; secondary outcome was encounters for asthma symptoms. Propensity scores were calculated for GLP-1R agonist and non-GLP-1R agonist use. Zero-inflated Poisson regression models included adjustment for multiple covariates. Measurements and Main Results: Patients initiating GLP-1R agonists (n=448), SGLT-2 inhibitors (n=112), DPP-4 inhibitors (n=435), sulfonylureas (n=2,253) or basal insulin (n=2,692), were identified. At six months, asthma exacerbation counts were lower in persons initiating GLP-1R agonists (reference) compared to SGLT-2 inhibitors (incidence rate ratio [IRR], 2.98 [95% CI, 1.30 to 6.80]), DPP-4 inhibitors (IRR, 2.45 [95% CI, 1.54 to 3.89]), sulfonylureas (IRR, 1.83 [95% CI, 1.20 to 2.77]) and basal insulin (IRR, 2.58 [95% CI, 1.72 to 3.88]). Encounters for asthma symptoms were also lower among GLP-1R agonist users. Conclusions: Adult asthmatics prescribed GLP-1R agonists for type 2 diabetes had lower counts of asthma exacerbations compared to other drugs initiated for treatment intensification. GLP-1R agonists may represent a novel treatment for asthma associated with metabolic dysfunction.

Comment on Albogami et al. Glucagon-Like Peptide 1 Receptor Agonists and Chronic Lower Respiratory Disease Exacerbations Among Patients With Type 2 Diabetes. Diabetes Care 2021;44:1344–1352

“…We read with interest the article by Albogami et al ( 1 ) on the association of glucagon-like peptide 1 receptor agonists (GLP-1RAs) and respiratory exacerbations among patients with asthma and/or chronic obstructive respiratory disease (COPD). In particular, the main conclusion that GLP-1RA initiation may be associated with a subsequent decrease in respiratory exacerbations echoes our findings recently published in the American Journal of Respiratory and Critical Care Medicine ( 2 ). Using electronic health records (EHR) of patients with asthma and comorbid type 2 diabetes, we found new initiators of GLP-1RAs had fewer asthma exacerbations than initiators of alternative step-up diabetes therapies in the 6 months following drug initiation.…”

The GLP-1 receptor in airway inflammation in asthma: a promising novel target?

“…Subsequently, a recent retrospective cohort study demonstrated a reduction in number of asthma exacerbations in patients with T2D on GLP-1R agonists compared to other antiglycemic agents (comparative incidence rate ratio ranged 1.83-2.98) [17]. Findings were robust even when accounting for changes in hemoglobin A1c and BMI, concurrent metformin use, and exposures to other antiglycemic agents.…”

The anti-inflammatory feature of glucagon-like peptide-1 and its based diabetes drugs -- Therapeutic potential exploration in lung injury

“…In a recent retrospective cohort study, Foer and colleagues compared rates of asthma exacerbations and symptoms between patients with T2D and asthma prescribed GLP-1RAs and those prescribed sodiumglucose cotransporter-2 (SGLT-2) inhibitors, or DPP-4 inhibitors, or sulfonylureas, or basal insulin. They observed that patients prescribed GLP-1RAs had lower counts of asthma exacerbation and encounters for asthma symptoms after 6 months of the treatment (105). In another human study, Mitchell and colleagues reported that GLP-1R is expressed in both human eosinophils and neutrophils but the numbers were reduced in allergic asthmatics (106).…”