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

Am J Respir Crit Care Med. 2021 Apr 1;203(7):831-840. doi: 10.1164/rccm.202004-0993OC.

Abstract

Rationale: GLP-1R (glucagon-like peptide-1 receptor) 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 adults with type 2 diabetes and asthma prescribed GLP-1R agonists and those prescribed SGLT-2 (sodium-glucose cotransporter-2) inhibitors, DPP-4 (dipeptidyl peptidase-4) inhibitors, sulfonylureas, or basal insulin for diabetes treatment intensification.Methods: This study was an 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 at an academic healthcare system from January 2000 to March 2018. The primary outcome was asthma exacerbations; the 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 6 months, asthma exacerbation counts were lower in persons initiating GLP-1R agonists (reference) compared with SGLT-2 inhibitors (incidence rate ratio [IRR], 2.98; 95% confidence interval [CI], 1.30-6.80), DPP-4 inhibitors (IRR, 2.45; 95% CI, 1.54-3.89), sulfonylureas (IRR, 1.83; 95% CI, 1.20-2.77), and basal insulin (IRR, 2.58; 95% CI, 1.72-3.88). Healthcare encounters for asthma symptoms were also lower among GLP-1R agonist users.Conclusions: Adult patients with asthma prescribed GLP-1R agonists for type 2 diabetes had lower counts of asthma exacerbations compared with other drugs initiated for treatment intensification. GLP-1R agonists may represent a novel treatment for asthma associated with metabolic dysfunction.

Keywords: antiasthmatic agents; diabetes mellitus type 2; electronic health records.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Asthma / chemically induced*
  • Asthma / drug therapy*
  • Asthma / epidemiology
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Female
  • Glucagon-Like Peptide-1 Receptor / agonists*
  • Glucagon-Like Peptide-1 Receptor / therapeutic use*
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Middle Aged
  • Retrospective Studies
  • Risk Factors
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use*
  • United States / epidemiology

Substances

  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Sodium-Glucose Transporter 2 Inhibitors