Repurposing glucagon-like peptide-1 receptor agonists for the treatment of neurodegenerative disorders

Authors

Marwan N. Sabbagh, Department of Neurology, Barrow Neurological Institute, Phoenix, AZ, USA. marwan.sabbagh@barrowneuro.org.
Jeffrey L. Cummings, Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, Kirk Kerkorian School of Medicine, University of Nevada, Las Vegas, NV, USA.
Clive Ballard, Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK.
Wiesje M. van der Flier, Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC, location VUmc, Amsterdam, Netherlands.
Michael T. Heneka, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg.
Jens Juul Holst, Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Lotte Bjerre Knudsen, Chief Scientific Advisor Office, Novo Nordisk A/S, Måløv, Denmark.
Stephen Salloway, Warren Alpert Medical School, Brown University, Providence, RI, USA.
Malú Gámez Tansey, Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA.
Daniel J. Drucker, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.

Document Type

Article

Abstract

With therapeutic progress in Alzheimer's disease (AD), more molecular and mechanistic targets are coming into focus. Beyond amyloid, emerging targets include tau, neuroinflammation and neurotransmitters. Targeting neuroinflammation in neurodegenerative diseases has been explored using cyclooxygenase inhibitors, but it has mostly been unsuccessful. Among the drug classes under investigation for AD are the glucagon-like peptide-1 receptor agonists (GLP-1RAs), which are approved for the treatment of type 2 diabetes (T2D), obesity and cardiovascular disease. GLP-1RAs are candidate treatments for AD based on several concepts. First, epidemiological data reveal that patients with T2D and cardiovascular disease receiving GLP-1RAs have substantial reductions in the risk of developing all-cause dementia. Second, GLP-1RAs reduce neuroinflammatory changes in preclinical models. Clinical trials have not yet shown that GLP-1RAs can slow the rate of cognitive decline in mild cognitive impairment and mild dementia due to AD. Here, we summarize data supporting the use of GLP-1RAs for the treatment of neurodegenerative diseases, with a focus on AD.

Publication Date

12-19-2025

Publication Title

Nature aging

E-ISSN

2662-8465

PubMed ID

41419667

Digital Object Identifier (DOI)

10.1038/s43587-025-01029-3

Recommended Citation

Sabbagh, Marwan N.; Cummings, Jeffrey L.; Ballard, Clive; van der Flier, Wiesje M.; Heneka, Michael T.; Holst, Jens Juul; Knudsen, Lotte Bjerre; Salloway, Stephen; Tansey, Malú Gámez; and Drucker, Daniel J., "Repurposing glucagon-like peptide-1 receptor agonists for the treatment of neurodegenerative disorders" (2025). Neurology. 2052.
https://scholar.barrowneuro.org/neurology/2052