{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:15:37Z","timestamp":1791227737095,"version":"4.1.0"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sepsis remains a leading cause of morbidity and mortality in critically ill patients, often complicated by sepsis-induced myopathy (SIM), systemic inflammation, and multiorgan dysfunction. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), initially developed for the treatment of type 2 diabetes, have demonstrated pleiotropic effects that may be beneficial in the septic context.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This review aims to explore the significance of GLP-1 receptors in the sepsis mechanism, as well as the therapeutic potential of GLP-1RAs in sepsis treatment, with a particular emphasis on their role in modulating inflammation, improving metabolic and endothelial function, and mitigating systemic inflammatory response syndrome (SIRS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A comprehensive synthesis of preclinical and clinical studies was conducted, focusing on the cellular mechanisms and systemic outcomes of GLP-1RA therapy in various models of sepsis and critical illness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>GLP-1RAs attenuate inflammation by suppressing NF-\u03baB and p38 MAPK pathways, reduce oxidative stress, enhance insulin sensitivity, and promote mitochondrial and endothelial stability. In skeletal muscle, they downregulate atrophy-associated genes (MuRF1, MAFbx) and upregulate myogenic factors (MyoD, MyoG), thereby improving perfusion and energy metabolism. Central GLP-1R signaling plays a crucial role in neuroimmune modulation and organ protection. Notably, these agents also increase adiponectin levels, which may further contribute to vascular integrity and anti-inflammatory effects during sepsis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>GLP-1RAs represent a novel and multifaceted therapeutic strategy for sepsis and its complications. They show promise as adjunctive therapy in sepsis due to their anti-inflammatory, antioxidant, and endothelial-protective actions. Experimental and limited clinical data suggest improved organ function and survival, but further human studies are needed to confirm efficacy, safety, and optimal treatment strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2025.1612034","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T06:31:45Z","timestamp":1763706705000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["The role of GLP-1 in the pathophysiology and treatment of sepsis: a narrative 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