REVIEW article
Front. Med.
Sec. Intensive Care Medicine and Anesthesiology
This article is part of the Research TopicSepsis Awareness Month 2024View all 7 articles
The Role of GLP-1 in the Pathophysiology and Treatment of Sepsis: A Narrative Review
Provisionally accepted
Nemanja Dimic*
Marko Djuric
Maja Vejapi
Irina Nenadic
Marina Bobos
Suzana BojicPredrag SavicMiljan Milanovic
Predrag Stevanovic- University Hospital Center Dr Dragiša Mišović, Belgrade, Serbia
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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.
Keywords: GLP-1 receptor agonists, Sepsis, muscle atrophy, Inflammation, Oxidative Stress
Received: 15 Apr 2025; Accepted: 24 Oct 2025.
Copyright: © 2025 Dimic, Djuric, Vejapi, Nenadic, Bobos, Bojic, Savic, Milanovic and Stevanovic. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Nemanja Dimic, nemanjadimic1989@gmail.com
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.