Glucagon-like Peptide-1 Receptor Agonists decrease type-2 biomarker in asthma
Dinah Foer1,2, Patrick Beeler3, Jing Cui1,2, Joshua A. Boyce1,2, Elizabeth Karlson1,2, David W. Bates1,2, Katherine Cahill4
1Brigham and Women's Hospital, 2Harvard Medical School, Boston, MA, 3University Hospital of Zurich, Zurich, Switzerland, 4Vanderbilt University Medical Center, Nashville, TN.
Glucagon-like peptide-1 receptor agonists (GLP-1RA) are approved for the treatment of type II diabetes mellitus (DMII) and obesity. In murine models, GLP-1RA inhibit allergen- and viral-induced airway inflammation including airway interleukin (IL)-33 release, IL-13 and mucus production and hyperresponsiveness. Observational patient data supports an association between GLP-1RA use and decreased asthma exacerbations in patients with asthma and DMII. We hypothesized that GLP-1RA would decrease biomarkers pertinent to airway inflammation pathways in patients with asthma. To test this hypothesis, we obtained serum samples from adults with asthma and comorbid DMII in the Partners HealthCare Biobank treated with (N=43) or without a GLP-1RA (N=119) at the time of sample collection. Demographics, body mass index, asthma severity, glucose control, and comorbidities, confirmed by electronic health record chart review were extracted and a propensity score calculated based on GLP-1RA use included as a covariate in a logistic regression model. Serum periostin, total IgE, IL-6, IL-8, IL-33 and sST2 levels were measured. Periostin (Padi=.0006) was significantly decreased in GLP-1RA users than non-GLP-1RA users which included use of basal insulin, SGLT-2 inhibitors or sulfonylureas. There were no significant differences in total IgE (Padj =.12), IL-6 (Padj =.62), IL-8 (Padj =.41), sCD163 (Padj=.53), IL-33 (Padj =.91), and sST2 (Padj =.90). Periostin results were robust across asthma severity and gender subgroup analyses. Serum periostin, a known systemic biomarker of Type (T)2 cytokines IL-4 and IL-13 in airway inflammation, is significantly and selectively decreased in adults with asthma and comorbid DMII treated with GLP-1RAs. Our results support a role for GLP-1R signaling in airway inflammation and point to periostin as a possible biomarker for therapeutic use of GLP-1RAs in asthma.
Funding: NIH AI118804, Brigham and Women’s Hospital Department of Medicine Innovation Evergreen Award, Brigham Research Institute Pilot Award