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Background: 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. Objective: 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). Methods: 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. Results: GLP-1RAs attenuate inflammation by suppressing NF-κB 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. Conclusion: 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.
Dimić et al. (Fri,) studied this question.