Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 May;38(5):355-373.
doi: 10.1007/s40266-021-00853-7. Epub 2021 Mar 19.

The Future of Incretin-Based Approaches for Neurodegenerative Diseases in Older Adults: Which to Choose? A Review of their Potential Efficacy and Suitability

Affiliations
Review

The Future of Incretin-Based Approaches for Neurodegenerative Diseases in Older Adults: Which to Choose? A Review of their Potential Efficacy and Suitability

Christine Girges et al. Drugs Aging. 2021 May.

Abstract

The current treatment options for neurodegenerative diseases in older adults rely mainly on providing symptomatic relief. Yet, it remains imperative to identify agents that slow or halt disease progression to avoid the most disabling features often associated with advanced disease stages. A potential overlap between the pathological processes involved in diabetes and neurodegeneration has been established, raising the question of whether incretin-based therapies for diabetes may also be useful in treating neurodegenerative diseases in older adults. Here, we review the different agents that belong to this class of drugs (GLP-1 receptor agonists, dual/triple receptor agonists, DPP-4 inhibitors) and describe the data supporting their potential role in treating neurodegenerative conditions including Parkinson's disease and Alzheimer's disease. We further discuss whether there are any distinctive properties among them, particularly in the context of safety or tolerability and CNS penetration, that might facilitate their successful repurposing as disease-modifying drugs. Proof-of-efficacy data will obviously be of the greatest importance, and this is most likely to be demonstrable in agents that reach the central nervous system and impact on neuronal GLP-1 receptors. Additionally, however, the long-term safety and tolerability (including gastrointestinal side effects and unwanted weight loss) as well as the route of administration of this class of agents may also ultimately determine success and these aspects should be considered in prioritising which approaches to subject to formal clinical trial evaluations.

PubMed Disclaimer

Similar articles

Cited by

References

    1. Ahmed RM, Devenney EM, Irish M, Ittner A, Naismith S, Ittner LM, et al. Neuronal network disintegration: common pathways linking neurodegenerative diseases. J Neurol Neurosurg Psychiatry. 2016;87:1234–41. - PubMed - PMC
    1. Ott A, Stolk RP, van Harskamp F, Pols HAP, Hofman A, Breteler MMB. Diabetes mellitus and the risk of dementia: the Rotterdam Study. Neurology. 1999;53:1937–1937.
    1. Sandyk R. The relationship between diabetes mellitus and Parkinson’s disease. Int J Neurosci. 1993;69:125–30. - PubMed
    1. Xu W, Caracciolo B, Wang H-X, Winblad B, Backman L, Qiu C, et al. Accelerated progression from mild cognitive impairment to dementia in people with diabetes. Diabetes. 2010;59:2928–35. - PubMed - PMC
    1. Mukherjee A, Morales-Scheihing D, Butler PC, Soto C. Type 2 diabetes as a protein misfolding disease. Trends Mol Med. 2015;21:439–49. - PubMed - PMC

Substances

LinkOut - more resources