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

Oct 29, 2025Biochemical and biophysical research communications

GLP-1 receptor activators may help both metabolism and inflammation in insulin resistance

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Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) may influence immune functions and suppress inflammation.

GLP-1RAs are associated with improved glycaemic management and weight loss in type 2 diabetes mellitus and obesity.
Evidence suggests that GLP-1RAs exhibit anti-inflammatory actions beyond their effects on glucose metabolism.
Low-grade inflammation may contribute to insulin resistance and metabolic syndrome.
GLP-1RAs may affect key signaling pathways involved in cellular stress responses and cytokine production.
These agents could serve as immunometabolic modulators by targeting both inflammatory and metabolic processes.

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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.

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

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