Overall description: This study will be a French, multicenter parallel groups, 2-arm, randomized, placebo-controlled, double-blind, proof-of-concept (POC) phase II trial evaluating the effect of lixisenatide, in patients with early PD. Justification: Parkinson's disease (PD) is a common neurodegenerative disease. Currently available symptomatic treatments allow improving motor and to a lesser extent non-motor function in PD patients. None of these treatments can slow down the underlining disease process and the relentless progression of motor and non-motor disability. Several mechanisms including the aggregation of misfolded alphasynuclein, mitochondrial dysfunction, oxidative stress and neuroinflammation have been related to the pathogenesis of PD. Recent evidence further suggests the implication of cerebral insulin resistance in the neurodegenerative process, while glucagon-like peptide 1 receptor (GLP1-R) agonists that are approved for the treatment of type 2 diabetes have neuroprotective properties in animal models of PD (Aviles-Olmos et al., 2013a). Moreover, the results of a recent clinical pilot trial suggest that treatment with the GLP-1R agonist exenatide for 12 months improves motor function in patients with moderate PD . GLP1-R are widely expressed in the central nervous system and GLP1-R agonists such as liraglutide, lixisenatide and exenatide have measurable brain concentrations, which makes them suitable for treating brain disorders. Lixisenatide is a well-tolerated GLP-1R agonist that can be administered once-daily (subcutaneous injection). It has demonstrated positive effects on learning and memory through an increase of hippocampal neurogenesis in preclinical models of obesity/diabetes. Furthermore, lixisenatide increases neurogenesis and decreases microglial activation in rodent models of Alzheimer's disease (APPswe/PS1ΔE9 mice and Aβ25-35 rats) (. At the same dose, lixisenatide showed higher effectiveness at activating brain GLP-1R than liraglutide and exenatide, and showed more effective neuroprotection in a variety of in-vitro models of neurodegeneration (WO2013/030409A1). Thus, this randomized, double-blind, clinical trial now aim to evaluate the effects of lixisenatide, versus placebo, on both motor and non-motor PD symptoms in patients at an early stage of PD. This study will involve centers of the French national Parkinson's disease and movement disorders research network (Ns-Park network).