GLP-1 receptor agonists and inflammatory pathway modulation: Dual targeting of metabolic and immune dysfunction in insulin resistance.

Because of their extensive effects on glycaemic management and weight loss, glucagon-like peptide-1 receptor agonists (GLP-1RAs) are showing promise as therapeutic agents in the treatment of type 2 diabetes mellitus (T2DM) and obesity. Their therapeutic use over the past few years is no longer restricted to glucose metabolism only, but increasingly, more evidence is suggesting their anti-inflammatory actions. Low-grade inflammation for prolonged periods is a important participant in the pathogenesis of insulin resistance and metabolic syndrome. It has been demonstrated that GLP-1RAs influence immune functions and suppress inflammation via influencing key signalling pathways, such as c-Jun N-terminal kinase (JNK), nuclear factor kappa B (NF-κB), and the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome. These signaling pathways are involved in cellular stress responses and cytokine production resulting in insulin resistance. By modulating both inflammatory and metabolic targets, GLP-1RAs are a potential class of immunometabolic modulators. This mini-review emphasizes the dual impact of GLP-1RAs and their therapeutic application in the overall management of insulin resistance and metabolic disorders.