Category: Parkinson’s Disease: Clinical Trials
Objective: To identify biological mechanisms that mediate Exenatide’s effect in the brain of patients with early Parkinson’s disease(PD).
Background: Tracking PD progression remains a major challenge due to lack of reliable biomarkers.GLP-1 receptor analogues are investigated, though their effects on the brain remain unclear. While early studies suggested Exenatide benefits motor symptom progression1,larger trials, including a UK phase-3 study2, 3,showed no effect.Lixisenatide slowed motor symptoms4,while Liraglutide benefited only non-motor symptoms5.These conflicting findings highlight the need for robust biomarkers.Alongside the UK trial, we investigated Exenatide’s mechanism in PD using multimodal assessments.
Method: FDG PET-based brain networks and plasma-derived metabolic and inflammatory markers were assessed in a randomized,double-blind,placebo-controlled trial. 59 patients received exenatide/placebo weekly for 18 months,followed by a 3-month washout. Of these,4 dropped out (2 SAEs unrelated to treatment,1 AE probably related,1 due to inconvenience). PD-related motor & cognitive metabolic patterns (PDRP & PDCP, respectively6) were quantified individually at baseline, 9, and 21 months. Statistics: mixed-effects ANCOVA models.
Results: 29 participants were randomly allocated to placebo and 26 to active treatment, with similar baseline characteristics.Over 21 months, Exenatide and Placebo groups showed significantly different changes of PDRP expression (p=0.01) across all three timepoints.Notably, a significant interaction effect at 9 months relative to baseline was present between groups (p=0.01; ANCOVA), with PDRP expression decreased in Exenatide but increased in Placebo group.A similar interaction effect was found for PDCP expression at 9 months (p<0.05; ANCOVA), but not over 21 months (p=0.11).Distinct responses in plasma-derived inflammatory and metabolic markers were also observed in Exenatide compared to Placebo. Nonetheless, MDS-UPDRS part 3 motor score in OFF and ON medication states did not differ between groups.
Conclusion: FDG-PET data reveals mechanistic evidence that Exenatide has distinct effects on mediating brain metabolic networks associated with both motor and cognitive deficits in PD. That said, such effects do not translate into clinical benefit, consistent with the recently completed phase-3 trial, and are not sustainable after treatment termination.
References: 1. Athauda, D., et al., Lancet 2017.
2. McGarry, A., et al., Lancet Neurol 2024, 23 (1), 37-45.
3. Vijiaratnam, N., et al., Lancet 2025.
4. Meissner, W. G., et al., N Engl J Med 2024, 390 (13), 1176-1185.
5. Hogg, E., et al., Lancet 2022, Available at SSRN: https://ssrn.com/abstract=4212371 or http://dx.doi.org/10.2139/ssrn.4212371.
6. Perovnik, M., et al., Nat Rev Neurol 2023, 19 (2), 73-90.
To cite this abstract in AMA style:
I. Markaki, CC. Tang, PE. Papathoma, L. Hainke, W. Paslawski, J. Paslawska, I. Savitcheva, U. Estenberg, D. Eidelberg, P. Svenningsson. Effect of Exenatide on disease progression in early Parkinson’s disease–a randomized, placebo controlled, single-center trial in Sweden [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/effect-of-exenatide-on-disease-progression-in-early-parkinsons-disease-a-randomized-placebo-controlled-single-center-trial-in-sweden/. Accessed October 5, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/effect-of-exenatide-on-disease-progression-in-early-parkinsons-disease-a-randomized-placebo-controlled-single-center-trial-in-sweden/