Glucagon-like peptide-1 receptor agonists (GLP-1RAs), originally developed and approved for the treatment of type 2 diabetes and obesity, are now demonstrating unprecedented therapeutic potential that extends beyond metabolic regulation alone. This review article aims to provide a comprehensive summary and analysis of the current state of knowledge regarding the expanding clinical horizons of GLP-1RAs, with a particular focus on their neuroprotective properties in Alzheimer’s disease (AD) and their use in the treatment of substance use disorders (SUDs), including alcohol dependence. Based on a systematic review of selected literature, including the latest preclinical studies and clinical trials, the multifaceted mechanisms of GLP-1 action in the central nervous system were analyzed. The accumulated evidence indicates that GLP-1 receptor agonists (GLP-1RAs) effectively cross the blood-brain barrier, alleviate systemic and local neuroinflammation, reduce oxidative stress, and improve synaptic plasticity. These effects translate into a halt in neuronal degeneration and beneficial cognitive outcomes in patients with early symptoms of AD. Furthermore, these drugs have been shown to innovatively modulate reward pathways in the brain (including the dopaminergic system), effectively reducing drug cravings, compulsive behaviors, and the consumption of alcohol and other addictive substances. In summary, the repurposing of GLP-1 receptor agonists represents an extremely promising strategy for treating complex neurological and psychiatric disorders. However, further large-scale clinical trials are necessary to optimize dosing protocols and confirm the long-term safety profile.
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Reczka et al. (2026) studied this question.
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