OBJECTIVES: The positive effects of exenatide on nerve cells raise the possibility that exenatide may slow down or stop Parkinson’s disease (PD) degeneration. The systematic literature review (SLR) aimed to identify and summarise the evidence supporting the efficacy and safety of exenatide in PD.

METHODS: EMBASE®, MEDLINE®, CENTRAL®, and clinicaltrial.gov were searched for English language articles published from inception to December 2022 evaluating the efficacy and safety of exenatide in PD. In accordance with various HTAs, the SLR followed two reviews and a quality control process.

RESULTS: Two randomized controlled trials (RCTs) conducted in the UK, met the inclusion criteria. A total of 107 patients (mean age: 57.2 years; Hoehn and Yahr stage between 1 to 2.5) were randomized to either exenatide or conventional PD treatments (control). At 48 weeks, a statistically significant improvement in MDS-UPDRS part 3 (off-medication) scores was observed with exenatide vs. control in both RCTs (RCT 1: CFB: -2.7 vs. +2.2, p=0.037; RCT 2: CFB: -2.3 vs. +1.7; p=0.0026). Further, in terms of MDS-UPDRS part 3 (on-medication) scores, exenatide suggested better improvement vs. the control group (RCT 1: -2.7 vs. +3.6 points) during the 48 weeks, however, results were comparable in another RCT (+1.1 vs +1.3). Both clinical trials showed well-tolerance to exenatide, however, weight loss, constipation, and injection sites were common adverse events (AE). Exenatide was associated with serious AEs, but none of them were related to the drug itself. The findings of the SLR suggested a promising future of exenatide in PD where results of 5 ongoing phase II/III trials are expected in 2023/2024.

CONCLUSIONS: Exenatide has demonstrated neuroprotective and neurorestorative properties in clinical settings, which makes it a potential treatment for PD patients. Considering the limited RCTs identified in the SLR, the results of ongoing trials will help to draw firm conclusions about exenatide's effectiveness and safety.