Neuroprotective potential of GLP-1 receptor agonists in Alzheimer’s disease: an integrative literature review

Abstract

Background: Alzheimer’s disease (AD) is the leading cause of dementia worldwide and represents a major public health challenge associated with population aging. It is characterized by β-amyloid plaque deposition, tau hyperphosphorylation, neuroinflammation, oxidative stress, and progressive neuronal loss. Increasing evidence suggests that impaired insulin signaling in the central nervous system contributes to AD pathophysiology. In this context, glucagon-like peptide-1 (GLP-1) receptor agonists, widely used in the treatment of type 2 diabetes mellitus, have emerged as potential neuroprotective agents. These drugs cross the blood–brain barrier and may reduce neuroinflammation, modulate insulin signaling, and decrease pathological protein aggregation, suggesting a possible role in Alzheimer’s disease therapy. Objective: To analyze recent evidence regarding the neuroprotective potential of GLP-1 receptor agonists in Alzheimer’s disease, focusing on underlying mechanisms and reported clinical outcomes. Methods: This integrative literature review was conducted using the PubMed/MEDLINE database in March 2026. The search strategy included the descriptors “GLP-1 receptor agonist” AND “Alzheimer’s disease” AND “neuroprotection”. Studies published between January 2020 and March 2026 were considered. Inclusion criteria comprised original research articles in English or Portuguese investigating neuroprotective effects of GLP-1 receptor agonists in Alzheimer’s disease, including randomized clinical trials, observational studies, and experimental studies in animal or cellular models. Reviews, editorials, and studies not directly related to neurodegeneration or cognitive outcomes were excluded. Study selection involved screening titles and abstracts followed by full-text analysis of eligible studies, with qualitative synthesis of the main findings. Results: The analyzed studies indicate that GLP-1 receptor agonists may exert neuroprotective effects through multiple mechanisms. Experimental models demonstrate reductions in β-amyloid accumulation, decreased tau hyperphosphorylation, attenuation of neuroinflammation, and reduced oxidative stress. Improvements in mitochondrial function, synaptic plasticity, and neuronal survival have also been reported. Preliminary clinical studies with agents such as liraglutide and semaglutide suggest improvements in cerebral glucose metabolism and possible slowing of cognitive decline, although the clinical evidence remains limited and heterogeneous. Conclusion: GLP-1 receptor agonists demonstrate promising neuroprotective potential in Alzheimer’s disease due to their ability to modulate insulin signaling, reduce neuroinflammation, and influence pathological protein aggregation. However, larger randomized clinical trials are required to confirm their therapeutic efficacy and define their role in clinical practice.