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. 2024 May 7;8(1):777-789.
doi: 10.3233/ADR-230181. eCollection 2024.

Clinical Evidence for GLP-1 Receptor Agonists in Alzheimer's Disease: A Systematic Review

Yulin Liang  1 , Vincent Doré  2   3 , Christopher C Rowe  3   4   5 , Natasha Krishnadas  3   5
Affiliations

Clinical Evidence for GLP-1 Receptor Agonists in Alzheimer's Disease: A Systematic Review

Yulin Liang et al. J Alzheimers Dis Rep. .

Abstract

Background: Alzheimer's disease (AD) is the most common cause of dementia. While preclinical studies have shown benefits of glucagon-like peptide 1 receptor agonists (GLP-1 RA) in targeting core AD pathology, clinical studies are limited.

Objective: A systematic review was performed to evaluate GLP-1 RAs in AD for their potential to target core AD pathology and improve cognition.

Methods: Searches were conducted via three different databases (PubMed, Embase, and Cochrane Library). Search terms included Medical Subject Headings (MeSH) terms: 'glucagon-like peptide 1 receptor agonist' and 'Alzheimer's disease', as well as entry terms 'GLP-1 RA', 'AD', and three types of GLP-1 RA: 'liraglutide', 'exenatide', and 'lixisenatide'.

Results: A total of 1,444 studies were screened. Six articles that met criteria were included (four randomized control trials [RCTs] and two protocol studies). Two RCTs with amyloid-β and tau biomarker endpoints did not observe an end of treatment difference between the placebo and treated groups. In three RCTs with cognitive endpoints, there was no end of treatment difference between placebo and treated groups. GLP-1 RA showed metabolic benefits, such as lower body mass index and improved glucose levels on oral glucose tolerance tests in treated groups. GLP-1 RA may mitigate the decline in cerebral glucose metabolism and show enhanced blood-brain glucose transport capacity using 18F-FDG PET, however, more data is needed.

Conclusions: GLP-1 RA therapy did not alter amyloid-β and tau biomarkers nor show improvements in cognition but showed potential metabolic and neuroprotective benefits.

Keywords: Alzheimer’s disease; amyloid; cognition; glucagon-like peptide 1; tau protein.

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Conflict of interest statement

Christopher C. Rowe has received research grants from NHMRC, Enigma Australia, Biogen, Eisai and Abbvie. He is on the scientific advisory board for Cerveau Technologies and has consulted for Prothena, Eisai, Roche, and Biogen Australia. All other authors have no conflict of interest to report.

Figures

Fig. 1
Fig. 1
PRISMA flowchart.
Fig. 2
Fig. 2
Risk of bias assessment.
See this image and copyright information in PMC

References

    1. Lane CA, Hardy J, Schott JM (2018) Alzheimer’s disease. Eur J Neurol 25, 59–70. - PubMed
    1. Du H, Meng X, Yao Y, Xu J (2022) The mechanism and efficacy of GLP-1 receptor agonists in the treatment of Alzheimer’s disease. Front Endocrinol (Lausanne) 13, 1033479. - PMC - PubMed
    1. Breijyeh Z, Karaman R (2020) Comprehensive review on Alzheimer’s disease: causes and treatment. Molecules 25, 5789. - PMC - PubMed
    1. Harris E (2023) Alzheimer drug lecanemab gains traditional FDA approval. JAMA 330, 495. - PubMed
    1. van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M, Kanekiyo M, Li D, Reyderman L, Cohen S, Froelich L, Katayama S, Sabbagh M, Vellas B, Watson D, Dhadda S, Irizarry M, Kramer LD, Iwatsubo T (2023) Lecanemab in early Alzheimer’s disease. N Engl J Med 388, 9–21. - PubMed

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