Immunometabolism and GLP-1 Signaling in Rheumatic Diseases: Molecular Mechanisms, Clinical Implications, and Therapeutic Perspectives
DOI:
https://doi.org/10.12775/QS.2026.68.74444Keywords
immunometabolism, GLP-1 receptor agonists, rheumatic diseases, rheumatoid arthritis, inflammation, metabolic reprogrammingAbstract
Background
Rheumatic diseases are increasingly recognized as disorders driven by both immune dysregulation and profound metabolic alterations. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), initially developed for obesity and type 2 diabetes, have demonstrated pleiotropic effects extending beyond metabolic control. However, the relationship between immunometabolism and GLP-1 signaling in rheumatic diseases remains incompletely understood.
Aim
To summarize current evidence on the interplay between immunometabolic pathways and GLP-1 signaling in rheumatic diseases.
Material and methods
A narrative review of studies published between 2010 and 2026 was conducted using the PubMed, Scopus, and Web of Science databases.
Results
Dysregulated glycolysis, mitochondrial dysfunction, altered lipid metabolism, and hypoxia-driven signaling contribute to chronic inflammation and tissue damage in rheumatic diseases. Key pathways involving AMP-activated protein kinase, mammalian target of rapamycin, hypoxia-inducible factor-1α, and the NLRP3 inflammasome link metabolism to immune activation. Beyond their glucose-lowering effects, GLP-1RAs modulate immune responses, attenuate inflammation, and improve cardiometabolic outcomes. Emerging evidence suggests potential benefits in rheumatoid arthritis, osteoarthritis, psoriasis, and other immune-mediated disorders.
Conclusions
Immunometabolism represents a promising therapeutic frontier in rheumatology, positioning GLP-1 signaling at the intersection of metabolism and immune homeostasis. Further mechanistic studies and clinical trials are needed to define the therapeutic role of GLP-1RAs in rheumatic diseases.
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