Exploring the role of glucagon-like peptide-1 receptor agonists in critical illness: mechanisms, benefits, and clinical implications.

Purpose of review: This review aims to synthesize current evidence on the expanding role of glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) beyond glycemic control, particularly in the context of critical illness. With growing recognition of their anti-inflammatory, immunomodulatory, and organ-protective properties, GLP-1RAs show promise in managing complications such as sepsis, acute respiratory distress syndrome (ARDS), acute kidney injury, and multiorgan dysfunction. This review explores their mechanisms across vital systems - including cardiovascular, pulmonary, renal, hepatic, neuropsychiatric, and gut-lung-microbiome axes - highlighting preclinical and clinical data. By consolidating emerging findings, this review aims to inform future translational research and support the integration of GLP-1RAs into critical care strategies.

Recent findings: Recent evidence highlights GLP-1RAs as promising adjuncts in critical illness due to their multiorgan protective effects. In cardiovascular systems, GLP-1RAs improve endothelial function, reduce ischemia-reperfusion injury, and modulate autonomic tone. In the CNS, they provide neuroprotection by reducing neuroinflammation and pyroptosis. In the lungs, they attenuate ARDS by decreasing cytokine production, enhancing surfactant secretion, and restoring alveolar-capillary integrity. Renally, they reduce acute injury and preserve filtration function. In the gut, GLP-1RAs modulate the microbiome, enhance barrier integrity, and lower systemic inflammation via the gut-lung axis. Additionally, they reduce hepatic inflammation and support pancreatic beta-cell survival, improving insulin sensitivity and metabolic stability in critical care.

Summary: GLP-1 receptor agonists hold promise as multiorgan protective agents in critical illness, offering benefits beyond glucose control. Their anti-inflammatory, metabolic, and vaso-protective properties may be harnessed to prevent or attenuate organ failure, support recovery, and improve long-term outcomes in critically ill patients. Further clinical trials are warranted to define their safety, efficacy, and optimal application across ICU populations.