Journal of Pharmaceutical Research · Jul 28, 2026
Anti-Inflammatory and Antioxidant Mechanisms of GLP-1 Receptor Agonists: Molecular Pathways and Therapeutic Implications
By Patil JH, Khairnar DJ, Donode SS et al.
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as important therapeutic agents in type 2 diabetes mellitus (T2DM) and obesity, with benefits extending beyond glycaemic control and weight reduction. Growing preclinical and clinical evidence indicates that GLP-1RAs exert significant anti-inflammatory and antioxidant effects through mechanisms that are partly independent of their glucose-lowering actions. This review comprehensively examines the molecular pathways underlying these pleiotropic effects and highlights their translational relevance across multiple organ systems. GLP-1RAs modulate inflammatory Signalling by inhibiting nuclear factor-kappa B (NF-κB) activation and suppressing NLRP3 inflammasome activity through cyclic AMP–protein kinase A (cAMP–PKA)-mediated pathways, thereby reducing the production of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6. In parallel, GLP-1RAs enhance cellular antioxidant defenses by activating the Nrf2/Keap1 pathway, inhibiting NADPH oxidase activity, and improving mitochondrial function, thereby reducing oxidative stress and lipid peroxidation. These effects contribute to cardioprotective, hepatoprotective, renoprotective, and neuroprotective outcomes observed in experimental and clinical studies. Furthermore, this review integrates current biomarker evidence with mechanistic insights to provide a comprehensive overview of the interconnected inflammatory and oxidative stress pathways targeted by GLP-1RAs. Collectively, these findings support the expanding therapeutic potential of GLP-1RAs in chronic inflammatory and metabolic disorders, including non-alcoholic steatohepatitis, chronic kidney disease, neurodegenerative diseases, and cardiovascular complications. Keywords: GLP-1 receptor, agonists, Inflammation, Oxidative stress, NF-κB, Nrf2/Keap1, cAMP–PKA pathway