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.

Rationale: Patients with chronic obstructive pulmonary disease (COPD) and type 2 diabetes (T2D) have worse clinical outcomes compared with patients without metabolic dysregulation. GLP-1 (glucagon-like peptide 1) receptor agonists (GLP-1RAs) reduce asthma exacerbation risk and improve FVC in patients with COPD. Objectives: To determine whether GLP-1RA use is associated with reduced COPD exacerbation rates, and severe and moderate exacerbation risk, compared with other T2D therapies. Methods: A retrospective, observational, electronic health records–based study was conducted using an active comparator, new-user design of 1,642 patients with COPD in a U.S. health system from 2012 to 2022. The COPD cohort was identified using a previously validated machine learning algorithm that includes a natural language processing tool. Exposures were defined as prescriptions for GLP-1RAs (reference group), DPP-4 (dipeptidyl peptidase 4) inhibitors (DPP-4is), SGLT2 (sodium-glucose cotransporter 2) inhibitors, or sulfonylureas. Measurements and Main Results: Unadjusted COPD exacerbation counts were lower in GLP-1RA users. Adjusted exacerbation rates were significantly higher in DPP-4i (incidence rate ratio, 1.48 [95% confidence interval, 1.08–2.04]; P = 0.02) and sulfonylurea (incidence rate ratio, 2.09 [95% confidence interval, 1.62–2.69]; P < 0.0001) users compared with GLP-1RA users. GLP-1RA use was also associated with significantly reduced risk of severe exacerbations compared with DPP-4i and sulfonylurea use, and of moderate exacerbations compared with sulfonylurea use. After adjustment for clinical covariates, moderate exacerbation risk was also lower in GLP-1RA users compared with DPP-4i users. No statistically significant difference in exacerbation outcomes was seen between GLP-1RA and SGLT2 inhibitor users. Conclusions: Prospective studies of COPD exacerbations in patients with comorbid T2D are warranted. Additional research may elucidate the mechanisms underlying these observed associations with T2D medications.

Mas-related G protein-couple receptor x2 (Mrgprx2) activation underlies many common non-IgE-mediated adverse drug reactions, yet the features of patients with reactions to Mrgprx2-activating drugs are unknown. To characterize the patient-specific comorbidities and laboratory characteristics associated with listed reactions to Mrgprx2-activating drugs, including fluoroquinolones, morphine, neuromuscular blockade agents, vancomycin and leuprolide. We used a retrospective, observational cohort study design, using electronic health record data from adults with an Mrgprx2-activating drug exposure recorded within a hospital system clinical Biobank. Odds ratios and incidence rate ratios for clinical characteristics associated with adverse drug reactions (ADR), including immediate hypersensitivity reactions, were calculated using multivariable logistic regression. Among 59,763 patients exposed to Mrgprx2-activating drugs, 4,846 had a listed ADR. Female sex, white race, asthma [OR 1.81, 95% CI (1.68 to 1.94)], chronic urticaria [OR 1.73, 95% CI (1.46 to 2.05)], and mastocytosis [OR 12.79, 95% CI (5.98 to 27.02)] were associated with increased odds of a reaction. Overall, patients with allergic disease had 1.21 times the rate of an ADR compared to patients without allergic disease. Elevated absolute eosinophil count was inversely associated with reactions and there was no association with elevated total IgE. Observed associations were similar in a patient subgroup with immediate type hypersensitivity reactions. Specific allergic diseases and common allergic biomarkers are differentially associated with ADRs to Mrgprx2-activating drugs. These findings from a large, “real world” drug-exposed population highlight clinical factors that may contribute to non-IgE mediated drug allergy.