GLP-1 AND DUAL GLP-1/GIP RECEPTOR AGONISTS AS NEUROPROTECTIVE AGENTS: MECHANISMS, CLINICAL EVIDENCE, AND TRANSLATIONAL PERSPECTIVES
DOI:
https://doi.org/10.31435/ijitss.3(51).2026.6110Keywords:
Brain Insulin Resistance, GLP-1 Receptor Agonists, Neuroinflammation, Alzheimer’s Disease, Parkinson’s Disease, Healthy AgingAbstract
Background: Neurodegenerative diseases are increasingly linked to metabolic dysfunction, such as impaired insulin signaling, mitochondrial dysfunction, oxidative stress, and chronic neuroinflammation. These observations have contributed to the type 3 diabetes hypothesis, which describes AD as a disorder associated with brain insulin resistance. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual GLP-1/GIP receptor agonists have emerged as promising therapeutic candidates because of their metabolic and neuroprotective properties.
Objective: To evaluate the neuroprotective potential of GLP-1 receptor agonists and dual GLP-1/GIP receptor agonists in neurodegenerative diseases.
Materials and Methods: A structured narrative review was conducted using PubMed, Scopus, and Web of Science databases. Studies published between 2015 and 2026 investigating incretin-based therapies in neurodegenerative disorders were included, encompassing randomized controlled trials, observational studies, meta-analyses, and mechanistic research.
Results: Preclinical studies consistently demonstrated neuroprotective effects of GLP-1RAs through modulation of neuroinflammation, oxidative stress, mitochondrial dysfunction, synaptic plasticity, and neuronal survival pathways. Observational studies suggested an association between incretin-based therapies and reduced dementia risk. Clinical trials in AD and PD have yielded heterogeneous results, with efficacy appearing to depend on disease stage and patient characteristics. Dual GLP-1/GIP receptor agonists showed promising mechanistic potential, although clinical evidence remains limited.
Conclusions: Incretin-based therapies represent a promising multi-target strategy for neurodegenerative diseases. Their effects extend beyond glycaemic regulation and may influence multiple pathways involved in neurodegeneration. Further large-scale clinical studies are required to determine their disease-modifying potential and optimal therapeutic use.
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Copyright (c) 2026 Beata Tekieli, Wojciech Krzysztof Cyran , Tatsiana Matsiusheuskaya, Weronika Cionżyńska , Krzysztof Machnik, Bartosz Gaweł, Anna Justkowska-Gebauer , Maksymilian Olesiński , Ewelina Chudyba , Michał Górecki
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