Category: Parkinson’s Disease: Clinical Trials
Objective: To evaluate the “disease-modifying” effect of lixisenatide as adjunct to antiparkinsonian medications in patients with early PD.
Background: Lixisenatide, a glucagon-like peptide 1 receptor (GLP1-R) agonist that crosses the blood-brain-barrier, is approved for treating type-2 diabetes and has neuroprotective properties in preclinical PD models. Two single-center phase II trials with other GLP-1R agonists (exenatide, liraglutide) have shown pilot beneficial effects on motor and non-motor outcomes in advanced PD.
Method: In this multicenter phase II trial run at 21 centers of the French NS-Park/FCRIN network, patients with early PD (< 3 years since diagnosis) on stable symptomatic medications without motor complications were randomized to receive subcutaneous injections of 20 µg lixisenatide or placebo once daily for 12 months, followed by a 2-month wash-out period. The primary endpoint was the change from baseline to month-12 in the MDS-UPDRS part III (motor examination) score in the ON condition. Secondary endpoints included: (a) mean changes from baseline in MDS-UPDRS I and II (motor and non-motor experiences of daily living) scores in ON (month-12), MDS-UPDRS III score in ON (month-6) and levodopa equivalent daily dosage (LEDD) (month-12); (b) mean MDS-UPDRS III score in the practically defined OFF condition at month-14 (end of wash-out) and (c) safety and tolerability.
Results: 156 patients were randomized (78 on placebo; 78 on lixisenatide; mean age=60 years, time from diagnosis=1.4 years, MDS-UPDRS III=15, LEDD=330 mg/d). Drop-out rate was low (4.5%). At month-12, MDS-UPDRS III score had increased significantly less on lixisenatide (0.0 [95%CI: -2 to 2]) than placebo (+3.0 [95%CI: 1 to 5]) (primary outcome; p=0.0068). At month-14, mean MDS-UPDRS III score in OFF was significantly lower on lixisenatide (17.7 [95%CI: 16 to 20] than placebo (20.6 [95%CI: 19 to 23]) (secondary outcome; p=0.0445). There was no between-group difference in other secondary outcomes including LEDD. Safety was in line with what is known in diabetes, with more frequent nausea on lixisenatide.
Conclusion: Lixisenatide had beneficial effects on motor progression in patients with early PD, supporting a disease-modifying effect that warrants further investigation.
To cite this abstract in AMA style:
WG. Meissner, P. Remy, C. Giordana, D. Maltete, P. Damier, JL. Houeto, C. Geny, L. Hopes, F. Durif, G. Defer, C. Tranchant, JC. Corvol, N. Carriere, JP. Azulay, S. Drapier, P. Krystkowiak, C. Thalamas, A. Benard, O. Rascol, N. Ns-Park/fcrin. Multicenter, randomized, placebo-controlled, double-blind, parallel-group proof-of-concept study of lixisenatide in patients with early Parkinson’s disease (PD): the LIXIPARK trial (NCT03439943) [abstract]. Mov Disord. 2023; 38 (suppl 1). https://www.mdsabstracts.org/abstract/multicenter-randomized-placebo-controlled-double-blind-parallel-group-proof-of-concept-study-of-lixisenatide-in-patients-with-early-parkinsons-disease-pd-the-lixipark-trial-nct0343994/. Accessed May 21, 2025.« Back to 2023 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/multicenter-randomized-placebo-controlled-double-blind-parallel-group-proof-of-concept-study-of-lixisenatide-in-patients-with-early-parkinsons-disease-pd-the-lixipark-trial-nct0343994/