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

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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.

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Authors and Affiliations

  1. Department of Clinical and Movement Neurosciences, UCL Institute of Neurology, London, UK

    Christine Girges, Nirosen Vijiaratnam, Dilan Athauda, Sonia Gandhi & Thomas Foltynie

  2. The National Hospital for Neurology and Neurosurgery, Queen Square, London, UK

    Christine Girges, Nirosen Vijiaratnam, Dilan Athauda, Sonia Gandhi & Thomas Foltynie

  3. Comprehensive Clinical Trials Unit, UCL, London, UK

    Grace Auld

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  1. Christine Girges
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Correspondence to Thomas Foltynie.

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CG reports no conflicts of interest. NV has received unconditional educational grants from IPSEN and Biogen, travel grants from IPSEN, AbbVie and The International Parkinson’s Disease and Movement Disorders Society, speaker’s honorarium from AbbVie and STADA and served on advisory boards for Abbvie and Brittania outside of the submitted work. DA has received travel grants from Bial. GA reports no conflicts of interest. SG reports no conflicts of interest. TF has received grants from National Institute of Health Research, Michael J Fox Foundation, John Black Charitable Foundation, Cure Parkinson’s Trust, Innovate UK, Van Andel Research Institute and Defeat MSA. He has served on Advisory Boards for Voyager Therapeutics, Handl therapeutics, Living Cell Technologies, Bial, and Profie Pharma. He has received honoraria for talks sponsored by Bial, Profile Pharma, and Boston Scientific.

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CG: Review of literature, preparation of manuscript, critical revision for intellectual content; NV: Interpretation of data, critical revision of manuscript for intellectual content; DA: Interpretation of data, critical revision of manuscript for intellectual content; GA: Critical revision of manuscript for intellectual content; SG: Critical revision of manuscript for intellectual content; TF: Article concept and design, interpretation of data, critical revision of manuscript for intellectual content.

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Girges, C., Vijiaratnam, N., Athauda, D. et al. The Future of Incretin-Based Approaches for Neurodegenerative Diseases in Older Adults: Which to Choose? A Review of their Potential Efficacy and Suitability. Drugs Aging 38, 355–373 (2021). https://doi.org/10.1007/s40266-021-00853-7

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