The Effectiveness of GLP-1 Receptor Agonists in Preventing and Managing Alzheimer’s Disease: A Systematic Review

Abstract

Background Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by memory loss, cognitive decline, and neuropathological features such as amyloid-beta plaques and tau tangles. GLP-1 receptor agonists (GLP-1RAs), primarily used for managing type 2 diabetes, have shown promise in preclinical studies as potential therapies for Alzheimer’s due to their neuroprotective effects. This systematic review aims to evaluate the effectiveness of GLP-1RAs in the prevention and management of Alzheimer’s disease.

Objective To systematically review and analyze the available clinical and preclinical evidence regarding the effectiveness of GLP-1 receptor agonists in preventing and managing Alzheimer’s disease, with a focus on cognitive outcomes, neurodegenerative biomarkers, and overall therapeutic potential.

Methods A comprehensive search was conducted in databases such as PubMed, Scopus, and Web of Science for studies published between 2010 and 2024. Studies were selected based on inclusion criteria of clinical trials, observational studies, and preclinical research involving GLP-1RAs in Alzheimer’s disease models or human patients with cognitive decline. Data on sample size, intervention details, cognitive and pathological outcomes, and methodological quality were extracted. A qualitative synthesis of the results was performed.

Results Six studies were included in this review, comprising both preclinical animal studies and clinical trials. Preclinical studies consistently demonstrated that GLP-1RAs reduced amyloid-beta plaque accumulation, tau pathology, and promoted neuronal survival, indicating a potential neuroprotective effect. However, clinical trials showed mixed results. Some studies (e.g., Gejl et al., 2016) observed preserved brain metabolism and slower brain atrophy with liraglutide, but cognitive improvements were modest and did not meet primary endpoints. Real-world observational studies indicated a reduced risk of dementia in populations using GLP-1RAs, particularly those with diabetes or obesity, suggesting additional benefits in metabolic pathways related to AD progression.

Conclusions The evidence suggests that GLP-1 receptor agonists have neuroprotective potential in Alzheimer’s disease, particularly based on preclinical findings. Clinical data, however, remains inconclusive, with inconsistent effects on cognition and cognitive decline. Further large-scale, long-term clinical trials with standardized endpoints are required to validate the therapeutic efficacy of GLP-1RAs in Alzheimer’s disease.