This study is a clinical trial in patients with Parkinson's disease (PD), of a drug called exenatide, which is already licensed for the treatment of patients with type 2 diabetes. There have been several groups that have confirmed that exenatide has beneficial effects of nerve cells when tested in the laboratory, which raises the possibility that exenatide may slow down or stop the degeneration of PD. In an open label trial in patients with PD who self administered the drug for a period of 48 weeks, the investigators have previously shown that the drug is well tolerated and shows encouraging effects on the movement and non-movement aspects of the disease. A double blind placebo controlled trial involving 60 participants was then conducted which indicated that exenatide may be a "neuroprotective" drug, i.e. one that stops the nerve cells dying in PD. The next step is therefore to confirm this "neuroprotective" effect and to see whether this effect can be reproduced in a multi-centre setting including a larger number of participants. An important objective is to explore whether any positive effects remain static or increase when the treatment is continued over a 96 week period. In order to explore this, a randomised, double blind, parallel group, placebo controlled, Phase 3 trial of Exenatide is being undertaken (Exenatide-PD3).

This study is a clinical trial in patients with Parkinson's disease (PD), of a drug called exenatide, which is already licensed for the treatment of patients with type 2 diabetes. There have been several groups that have confirmed that exenatide has beneficial effects of nerve cells when tested in the laboratory, which raises the possibility that exenatide may slow down or stop the degeneration of PD. In an open label trial in patients with PD who self administered the drug for a period of 48 weeks, investigators have previously shown that the drug is well tolerated and shows encouraging effects on the movement and non-movement aspects of the disease. A double blind placebo controlled trial involving 60 participants was then conducted which indicated that exenatide may be a "neuroprotective" drug, i.e. one that stops the nerve cells dying in PD. The next step is therefore to confirm this "neuroprotective" effect and to see whether this effect can be reproduced in a multi-centre setting including a larger number of participants. An important objective is to explore whether any positive effects remain static or increase when the treatment is continued over a 96 week period.

Inclusion Criteria:

1. Diagnosis of Parkinson's disease.
2. Hoehn and Yahr stage ≤2.5 in the ON medication state.
3. Between 25 and 80 years of age.
4. On dopaminergic treatment for at least 4 weeks before enrolment.
5. Ability to self-administer, or to arrange carer administration of trial medication.
6. Documented informed consent to participate.

Exclusion Criteria:

1. Diagnosis or suspicion of other cause for Parkinsonism.
2. Patients unable to attend the clinic visits in the practically defined OFF medication state.
3. Body mass index <18.5.
4. Known abnormality on CT or MRI brain imaging considered likely to compromise compliance with trial protocol.
5. Significant cognitive impairment defined by a score <21 on the Montreal Cognitive Assessment.
6. Concurrent severe depression defined by a score ≥16 on the Patient Health Questionnaire (PHQ-9).
7. Prior intra-cerebral surgical intervention for Parkinson's disease.
8. Previous participation in one of the following Parkinson's disease trials (Biogen SPARK trial, Prothena Pasadena trial, Sanofi Genzyme MOVES-PD trial, UDCA-PD UP Study or any other trial still considered to involve a potentially PD modifying agent).
9. Participation in another clinical trial of a device, drug or surgical treatment within the last 30 days
10. Previous exposure to exenatide.
11. Impaired renal function with creatinine clearance <50ml/min.
12. History of pancreatitis.
13. Type 1 or Type 2 diabetes mellitus.
14. Severe gastrointestinal disease (e.g. gastroparesis)
15. Hyperlipidaemia.
16. History or family history of medullary thyroid cancer (MTC).
17. Multiple endocrine neoplasia 2 (MEN2) syndrome.
18. Hypersensitivity to any of exenatide's excipients.
19. Females that are pregnant or breast feeding.
20. WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire trial period and up to 3 months after the last dose of trial medication.
21. Participants who lack the capacity to give informed consent
22. Any medical or psychiatric condition or previous conventional/experimental treatment which in the investigator's opinion compromises the potential participant's ability to participate.

Double Blind