Neuroprotective Effects of Semaglutide: A Comprehensive Review of Cognitive Function and Neuroinflammation (Atena Editora)

Abstract

INTRODUCTION Semaglutide, a GLP-1 receptor agonist, has demonstrated significant potential in managing type 2 diabetes mellitus (T2DM) and offers promising neuroprotective benefits. Its structure allows it to mimic endogenous GLP-1, which plays a crucial role in modulating insulin secretion and glucose metabolism. Beyond metabolic regulation, semaglutide impacts the central nervous system (CNS), particularly in regions associated with cognition and neuroprotection. Evidence shows that GLP-1 receptor activation by semaglutide can enhance synaptic plasticity, reduce neuroinflammation, and promote neuronal survival, making it a potential therapeutic agent for cognitive decline and neurodegenerative diseases. OBJETIVE To analyze the neuroprotective effects of semaglutide, focusing on its impact on cognitive function and neuroinflammation in both preclinical and clinical settings. METHODS This is a narrative review which included studies in the MEDLINE – PubMed (National Library of Medicine, National Institutes of Health), COCHRANE, EMBASE and Google Scholar databases, using as descriptors: “Neuroprotection” AND “GLP-1 Receptor Agonists” AND Cognitive Function” OR “Neuroinflammation” OR “Diabetes and Brain Health” in the last years. RESULTS AND DISCUSSION Extensive preclinical studies have shown that semaglutide improves cognitive function and reduces neuroinflammation in rodent models of cognitive impairment. These effects are attributed to semaglutide's ability to enhance synaptic plasticity, promote neurogenesis, and modulate neuroinflammatory pathways. Clinical trials have further supported these findings, demonstrating significant improvements in cognitive performance among diabetic patients treated with semaglutide. The drug's capacity to cross the blood-brain barrier and exert direct CNS effects is critical for its neuroprotective benefits. Comparative studies indicate that semaglutide offers superior neuroprotection compared to other GLP-1 receptor agonists, due to its longer half-life and greater potency. Additionally, semaglutide has been shown to reduce biomarkers of neuroinflammation and oxidative stress, contributing to its overall efficacy in preserving cognitive function and potentially modifying the progression of neurodegenerative diseases. CONCLUSION Semaglutide represents a significant advancement in neuroprotection, providing therapeutic benefits that extend beyond glycemic control in diabetes. Its ability to modulate neuroinflammation, oxidative stress, synaptic plasticity, and neurogenesis underpins its potential to improve cognitive outcomes and protect against neurodegenerative diseases. Future research should focus on elucidating the molecular pathways influenced by semaglutide, optimizing its use in neurodegenerative conditions, and exploring its efficacy in non-diabetic populations at risk for cognitive decline. Semaglutide's diverse mechanisms of action and proven efficacy make it a valuable addition to treatments aimed at preserving brain health and enhancing the quality of life for patients with diabetes and beyond.