The Future of Incretin-Based Approaches for Neurodegenerative Diseases in Older Adults: Which to Choose? A Review of their Potential Efficacy and Suitability
- PMID: 33738783
- DOI: 10.1007/s40266-021-00853-7
The Future of Incretin-Based Approaches for Neurodegenerative Diseases in Older Adults: Which to Choose? A Review of their Potential Efficacy and Suitability
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.
Similar articles
-
Incretin-based therapy for type 2 diabetes mellitus is promising for treating neurodegenerative diseases.Rev Neurosci. 2016 Oct 1;27(7):689-711. doi: 10.1515/revneuro-2016-0018. Rev Neurosci. 2016. PMID: 27276528 Review.
-
Incretin-based therapies for type 2 diabetes mellitus: a review of direct comparisons of efficacy, safety and patient satisfaction.Int J Clin Pharm. 2013 Apr;35(2):159-72. doi: 10.1007/s11096-012-9729-9. Epub 2012 Dec 22. Int J Clin Pharm. 2013. PMID: 23263796 Review.
-
Risk of heart failure hospitalization among users of dipeptidyl peptidase-4 inhibitors compared to glucagon-like peptide-1 receptor agonists.Cardiovasc Diabetol. 2018 Jul 17;17(1):102. doi: 10.1186/s12933-018-0746-4. Cardiovasc Diabetol. 2018. PMID: 30016946 Free PMC article.
-
Differentiating among incretin therapies: a multiple-target approach to type 2 diabetes.J Clin Pharm Ther. 2012 Oct;37(5):510-24. doi: 10.1111/j.1365-2710.2012.01342.x. Epub 2012 Mar 21. J Clin Pharm Ther. 2012. PMID: 22436069 Review.
-
CARDIOVASCULAR OUTCOME TRIALS OF THE INCRETIN-BASED THERAPIES: WHAT DO WE KNOW SO FAR?Endocr Pract. 2017 Jan;23(1):89-99. doi: 10.4158/EP161481.RA. Epub 2016 Nov 7. Endocr Pract. 2017. PMID: 27819769 Review.
Cited by
-
How should we be using biomarkers in trials of disease modification in Parkinson's disease?Brain. 2023 Dec 1;146(12):4845-4869. doi: 10.1093/brain/awad265. Brain. 2023. PMID: 37536279 Free PMC article.
-
DPP-4 inhibitors sitagliptin and PF-00734,200 mitigate dopaminergic neurodegeneration, neuroinflammation and behavioral impairment in the rat 6-OHDA model of Parkinson's disease.Geroscience. 2024 Oct;46(5):4349-4371. doi: 10.1007/s11357-024-01116-0. Epub 2024 Apr 2. Geroscience. 2024. PMID: 38563864 Free PMC article.
-
Nanotechnology-Based Drug Delivery Strategies to Repair the Mitochondrial Function in Neuroinflammatory and Neurodegenerative Diseases.Pharmaceutics. 2021 Dec 1;13(12):2055. doi: 10.3390/pharmaceutics13122055. Pharmaceutics. 2021. PMID: 34959337 Free PMC article. Review.
-
Metabolic hormones are integral regulators of female reproductive health and function.Biosci Rep. 2024 Jan 31;44(1):BSR20231916. doi: 10.1042/BSR20231916. Biosci Rep. 2024. PMID: 38131197 Free PMC article. Review.
References
-
- 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.
-
- Sandyk R. The relationship between diabetes mellitus and Parkinson’s disease. Int J Neurosci. 1993;69:125–30. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Miscellaneous