GLP-1 as a Regulator of Oxidative Signalling in Metabolic Health and Disease

Glucagon-like peptide-1 (GLP-1) has emerged as a key regulator of metabolic, inflammatory and oxidative homeostasis, extending beyond its traditional function as an incretin hormone. This narrative review summarises the latest evidence from two decades of research into the role of GLP-1 in redox biology and metabolic regulation in tissues affected by obesity, type 2 diabetes and metabolic dysfunction-associated steatotic liver disease. There is growing evidence that GLP-1 signalling modulates multiple oxidative pathways, including AMPK-dependent metabolic reprogramming, mitochondrial quality control, nitric oxide-cGMP signalling, the regulation of ferroptosis, and the suppression of inflammatory pathways such as the NLRP3 inflammasome. Through these mechanisms, GLP-1 contributes to maintaining cellular redox balance, mitochondrial resilience, and metabolic adaptation in conditions of chronic oxidative stress. The review also emphasises the complementary function of GLP-1 receptor agonists (GLP-1RAs) and natural bioactive compounds such as polyphenols, anthocyanins, terpenoids and omega-3 fatty acids. These compounds may reinforce antioxidant defences, reduce inflammatory signalling and support mitochondrial function. Particular attention is given to the role of the gut microbiota in determining GLP-1 responsiveness. Gut microbiota-derived metabolites, including short-chain fatty acids (SCFAs) and bile acid derivatives, contribute to incretin secretion, intestinal barrier maintenance, and systemic redox regulation. This review integrates endocrinology, oxidative stress biology, microbiome science and nutritional biochemistry to provide a comprehensive framework describing GLP-1 as a multi-organ metabolic signal that coordinates endocrine, immune, mitochondrial and redox pathways. These insights will inform the development of future therapeutic strategies that combine GLP-1-based pharmacology with precision nutrition and microbiome-targeted approaches, with the aim of improving metabolic resilience and addressing the oxidative dysregulation associated with chronic metabolic diseases.