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GLP-1-based therapies in lung diseases
Marissa O'Callaghan1, Mariëtte R Boon2, Gert-Jan Braunstahl3,4
1Department of ILD, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Abstract:
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), initially developed for the treatment of type 2 diabetes and obesity, are increasingly recognised as multi-system agents with cardiovascular, renal and anti-inflammatory benefits. Emerging evidence suggests that their pleiotropic metabolic and immunomodulatory effects may have therapeutic relevance in chronic lung diseases. The lung is a metabolically active organ in which obesity, insulin resistance and systemic inflammation contribute to disease susceptibility, progression and treatment response. Chronic lung diseases such as asthma, COPD, pulmonary hypertension and interstitial lung disease share overlapping inflammatory, vascular and fibrotic pathways that may be modifiable through GLP-1 RA-based therapies. Preclinical studies demonstrate that GLP-1R signalling influences airway inflammation, oxidative stress, endothelial function and fibroblast activation. Observational and early clinical data suggest potential benefits in asthma control, exacerbation reduction in COPD, vascular remodelling in pulmonary hypertension and a reduction in all-cause mortality in interstitial lung disease. In addition to weight loss and glycaemic improvement, GLP-1 RAs exert direct anti-inflammatory and immune-regulatory effects that may act independently of metabolic change. Despite promising mechanistic and translational signals, high-quality randomised controlled trials with GLP-1 RAs in pulmonary populations remain limited. Key questions include patient selection, interaction with established anti-inflammatory and antifibrotic therapies, and the relative contribution of metabolic versus direct pulmonary effects. This review aims to synthesise current mechanistic, experimental and clinical evidence supporting GLP-1 RA use in chronic lung disease and outlines future research priorities within a precision-medicine framework.
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