Ashley Y Wu1, Katherine N Cahill1,2, Shinji Toki1,2, R Stokes Peebles1,2,3,4. 1. Department of Medicine. 2. Division of Allergy, Pulmonary, and Critical Care Medicine. 3. Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine. 4. Tennessee Valley Healthcare System, United States Department of Veterans Affairs, Nashville, Tennessee, USA.
Abstract
PURPOSE OF REVIEW: The aim of this study was to discuss the role of glucagon-like peptide-1 (GLP-1) receptor signalling in reducing lung inflammation and potential use for GLP-1 receptor agonists (GLP-1RAs) in management of asthma. RECENT FINDINGS: Although GLP-1RA are currently used for the treatment of type 2 diabetes (T2D) and weight loss in obesity, there is much interest in expanding the indications for use in other diseases, including inflammatory pulmonary disease. In animal models of both acute and chronic pulmonary disease, use of GLP-1RA reduces airway inflammation, obstruction and fibrosis. In particular, GLP-1 receptor (GLP-1R) signalling seems to inhibit allergen-induced type 2 inflammation, making it an attractive agent for asthma. Results are especially promising in disease processes with disturbed metabolic regulation, such as T2D or metabolic syndrome. Retrospective clinical studies demonstrate promising evidence for the use of GLP-1RAs in comorbid diabetes and asthma, although prospective human studies are limited. SUMMARY: Here, we discuss the biology of GLP-1 and GLP-1R signalling, review the preclinical and mechanistic evidence for how GLP-1R signalling may reduce pulmonary inflammation, and summarize recent and upcoming clinical studies. Ultimately, targeting GLP-1R signalling may represent a novel approach for asthma therapy that is glucocorticoid sparing and possibly disease modifying.
PURPOSE OF REVIEW: The aim of this study was to discuss the role of glucagon-like peptide-1 (GLP-1) receptor signalling in reducing lung inflammation and potential use for GLP-1 receptor agonists (GLP-1RAs) in management of asthma. RECENT FINDINGS: Although GLP-1RA are currently used for the treatment of type 2 diabetes (T2D) and weight loss in obesity, there is much interest in expanding the indications for use in other diseases, including inflammatory pulmonary disease. In animal models of both acute and chronic pulmonary disease, use of GLP-1RA reduces airway inflammation, obstruction and fibrosis. In particular, GLP-1 receptor (GLP-1R) signalling seems to inhibit allergen-induced type 2 inflammation, making it an attractive agent for asthma. Results are especially promising in disease processes with disturbed metabolic regulation, such as T2D or metabolic syndrome. Retrospective clinical studies demonstrate promising evidence for the use of GLP-1RAs in comorbid diabetes and asthma, although prospective human studies are limited. SUMMARY: Here, we discuss the biology of GLP-1 and GLP-1R signalling, review the preclinical and mechanistic evidence for how GLP-1R signalling may reduce pulmonary inflammation, and summarize recent and upcoming clinical studies. Ultimately, targeting GLP-1R signalling may represent a novel approach for asthma therapy that is glucocorticoid sparing and possibly disease modifying.
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