GLP-1 as a regulator of sepsis outcomes: Insights into cellular metabolism, inflammation, and therapeutic potential

Glucagon-like peptide-1 (GLP-1) has been widely studied in the context of treating obesity and various forms of metabolic disease. Sepsis is a life-threatening medical emergency characterized by the widespread dysregulation of energy metabolism within cells. The potential for GLP-1 to improve sepsis patient outcomes through improvements in energy metabolism and inflammation has been a focus of growing research interest, with many studies of GLP-1 itself and related compounds, including GLP-1 receptor agonists (GLP-1RAs), and dipeptidyl peptidase-4 (DPP-4) inhibitors, having explored the impact on sepsis in cells and organs. Such studies require that attention be paid to both the physiological and potential pathological effects of GLP-1 in sepsis. In many reports, researchers have demonstrated that endogenous GLP-1, GLP-1RAs, or DPP-4 inhibitors (a GLP-1 depressant) can modulate glucose homeostasis, inflammatory activity, immune function, and organ dysfunction in studies of sepsis model systems in vitro and in vivo. To date, GLP-1-based treatments have yet to be specifically used to manage sepsis, but its pleiotropic effects suggest its significant potential in sepsis treatment. This review provides an overview of the relationship between GLP-1 and its related compounds with sepsis, aiming to offer novel perspectives for the diagnosis and treatment of this condition. It highlights that GLP-1 may serve as a new biomarker for assessing the severity and prognosis of sepsis, and potentially contribute to improving clinical outcomes in septic patients. Meanwhile, GLP-1 may function as a messenger of metabolic reprogramming, shifting cellular energy production from oxidative phosphorylation to glycolysis, thereby modulating immune responses and influencing inflammatory reactions to enhance the clearance of pathogens. However, GLP-1 may act as a double-edged sword, the enhanced inflammatory response can potentially induce cytotoxic and organ-damaging effects while exerting beneficial actions.