The role of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors in chronic obstructive pulmonary disease.

INTRODUCTION: Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of morbidity and mortality worldwide, with type 2 diabetes mellitus (T2DM), obesity, and cardiovascular disease being common co-morbidities associated with worse outcomes. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors, which were originally developed for treatment of T2DM and/or obesity, have recently been shown to reduce exacerbations in observational studies of patients with COPD, suggesting that repurposing GLP-1RAs and SGLT2 inhibitors could improve clinical outcomes in COPD.

AREAS COVERED: COPD, diabetes, and obesity share several common inflammatory pathways, including macrophage dysfunction, inflammasome activation, and metabolic dysregulation. Here we review the pharmacology, pre-clinical, and emerging clinical data which could support repurposing of GLP-1RAs and SGLT2 inhibitors for use in COPD through a search of articles in PubMed and Medline from 01/1950 to 08/2025.

EXPERT OPINION: Reevaluating metabolic therapeutic targets has the potential to redefine treatment strategies for patients with COPD and metabolic comorbidities. Potential mechanisms of action could be via modulation of the NLRP3 inflammasome and macrophage polarization or better control of co-morbid conditions. However, randomized controlled trials and mechanistic studies are needed to confirm these observational findings and elucidate underlying mechanisms.