Objective: To provide a comprehensive narrative review of the mechanistic rationale and clinical evidence for GLP-1 RA use across the spectrum of movement disorders, including Parkinson’s disease (PD), multiple system atrophy (MSA), Huntington’s disease (HD), essential tremor, Lewy body dementia, and drug-induced movement disorders.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) — best known as treatments for type 2 diabetes and obesity — have attracted growing interest as candidates for neuroprotection in movement disorders. Their receptors are widely expressed in the substantia nigra, striatum, cerebellum, and other motor-relevant brain regions.

Method: A narrative review of published literature from PubMed/MEDLINE, EMBASE, and ClinicalTrials.gov up to February 2026 was performed.

Results: Evidence is strongest for PD, where multiple phase II RCTs — notably the LIXIPARK trial — demonstrate motor slowing and biomarker improvements. Emerging data in MSA support a disease-modifying signal. In HD, preclinical models show motor benefit and survival advantage. Mechanistically, GLP-1 RAs reduce neuroinflammation, oxidative stress, alpha-synuclein aggregation, and mitochondrial dysfunction across models. Safety signals, including a pharmacovigilance-detected tremor-risk signal, require monitoring.

Conclusion: GLP-1 RAs represent a paradigm-shifting class for movement disorders, offering a shared neuroprotective mechanism applicable across nosological boundaries. Phase III trials are urgently needed, and movement disorder specialists should be engaged in their design.

References: 1. Meissner WG, Remy P, Giordana C, Maltête D, Derkinderen P, Houéto JL, Anheim M, Benatru I, Boraud T, Brefel-Courbon C, Carrière N. Trial of lixisenatide in early Parkinson’s disease. New England journal of medicine. 2024 Apr 4;390(13):1176-85.
2. Vijiaratnam N, Girges C, Wiegand M, Ismail C, Lameirinhas A, Yarnall A, Kirk C, Del‐Din S, Rochester L, Kobylecki C, Ambler G. Exenatide Once Weekly in the Treatment of Patients with Multiple System Atrophy. Annals of neurology. 2025 Nov;98(5):991-1003.
3. Hölscher C. Incretin Hormones GLP-1 and GIP Normalize Energy Utilization and Reduce Inflammation in the Brain in Alzheimer’s Disease and Parkinson’s Disease: From Repurposed GLP-1 Receptor Agonists to Novel Dual GLP-1/GIP Receptor Agonists as Potential Disease-Modifying Therapies: C. Hölscher. CNS drugs. 2025 Dec;39(12):1201-20.
4. De Giorgi R, Ghenciulescu A, Dziwisz O, Taquet M, Adler AI, Koychev I, Upthegrove R, Solmi M, McCutcheon R, Pillinger T, Cowen PJ. An analysis on the role of glucagon-like peptide-1 receptor agonists in cognitive and mental health disorders. Nature Mental Health. 2025 Mar;3(3):354-73.

« Back to 2026 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/glp-1-receptor-agonists-in-movement-disorders-from-parkinsons-disease-to-the-broader-spectrum-mechanisms-evidence-and-future-directions/