Athauda 2017.

Study characteristics
Methods	Study design: randomised, double‐blind, placebo‐controlled, parallel‐group study Duration of study: participants were followed up at 60 weeks Number of centres: 1 Location: London, UK Study setting: research/tertiary care facility Withdrawals: 2 participants before 12 weeks (I = 1, C = 1), both excluded from analysis Discontinued treatment: 3 participants (I = 1, C = 2). All continued follow‐up assessments as per protocol Compliance: assessed as "very high: 58 patients reported not missing a single dose" Dates of study: June 2014 to August 2016 (from ClinicalTrials.gov; https://clinicaltrials.gov/ct2/show/NCT01971242)
Participants	Number of participants: 62 randomised, 2 withdrawals, so 60 included in analysis (I = 31, C = 29) Age in years, mean (SD): intervention: 61.6 (8.2), control: 57.8 (8.0) Gender, N (%): intervention: female 9 (29%), male 22 (71%); control: female 7 (24%), male 22 (76%) Duration of diagnosis at baseline, years (SD): intervention: 6.4 (3.3); control: 6.4 (3.3) Severity of condition, N (%): Hoehn and Yahr stage 1.0 to 2.0: intervention: 29 (94%); control: 29 (100%) Hoehn and Yahr stage 2.5: intervention: 2 (6%); control: 0 (0%) Study inclusion criteria: Men and women Aged 25 to 75 years Idiopathic Parkinson's disease as measured by Queen Square Brain Bank criteria On dopaminergic treatment with wearing‐off effects Judged able to administer the trial drug or to arrange carer administration of the trial drug At Hoehn and Yahr stage 2.5 or less when on treatment Study exclusion criteria: Diagnosis or suspicion of other cause for parkinsonism (i.e. patients with clinical features indicating a diagnosis of progressive supranuclear palsy, multiple systems atrophy, drug‐induced parkinsonism, dystonic tremor, or essential tremor), lack of DaTSCAN appearance consistent with diagnosis of PD Body mass index < 18.5 Known abnormality on CT or MRI brain imaging considered likely to compromise compliance with trial protocol/DaTSCAN acquisition Concurrent dementia defined by a score < 120 on the Mattis Dementia Rating Scale Concurrent severe depression defined by a score > 16 on the MADRS Prior intracerebral surgical intervention for Parkinson’s disease Already actively participating in a trial of a device, drug, or surgical treatment for Parkinson’s disease Previous exposure to exenatide Type 1 or type 2 diabetes mellitus Severely impaired renal function with creatinine clearance < 30 mL/min Hyperlipidaemia History of pancreatitis Severe gastrointestinal disease (e.g. gastroparesis) History or suspicion of thyroid cancer Known or suspected intolerance of DaTSCAN or potassium iodide administration Female who is pregnant or breastfeeding Individuals who lack the capacity to give informed consent Any medical or psychiatric condition that in the investigator’s opinion compromises the ability of the potential participant to participate
Interventions	Intervention: self‐administered exenatide 2 mg via subcutaneous injection once weekly for 48 weeks + regular drugs Comparator: self‐administered placebo via subcutaneous injection once weekly for 48 weeks + regular drugs
Outcomes	Primary: MDS‐UPDRS part III scores in the practically defined off‐medication state at 60 weeks Secondary: differences at 48 and 60 weeks between groups for: each subsection of MDS‐UPDRS (on medication); scores on the Unified Dyskinesia Rating Scale, the Montgomery and Åsberg Depression Rating Scale, the Non‐Motor Symptoms Severity Scale, the Parkinson’s Disease 39‐item Quality of Life Questionnaire, and the Mattis Dementia Rating Scale (on medication); dopamine transporter availability as measured by DaTSCAN; 13 timed motor tests in both off‐medication and on‐medication states; levodopa equivalent dose; and 3‐day Hauser diary of Parkinson’s disease state
Notes	Funding: Michael J Fox Foundation for Parkinson Disease Interests: AJL reports grants from the Frances and Renee Hock Fund, consulting fees from Britannia Pharmaceuticals (Genus) and BIAL Portela, and honoraria from Profile Pharma, Teva, Lundbeck, BIAL, Roche, Britannia, UCB, Nordiclnfu Care, NeuroDerm, and Decision Resources TTW has received honoraria from Britannia Pharmaceuticals PL has received honoraria from Medtronic and St Jude Medical NHG is a named inventor on a National Institutes of Health patent describing the use of GLP‐1 RAs in neurodegenerative disorders TF has received honoraria from Profile Pharma, BIAL, AbbVie, Genus, Medtronic, and St Jude Medical
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	“We used SealedEnvelope, an independent, commercial, Internet‐based randomisation service that generated the online randomisation list on the basis of guidance from the trial IT manager (SH) and trial statistician (SSS)”
Allocation concealment (selection bias)	Low risk	"SealedEnvelope will provide a unique trial identification code for each recruited participant. ……At the baseline visit, the clinical investigator will enter the patient’s initials, gender, date of birth, date of consent, criteria fulfilment, and PD severity strata into the SealedEnvelope.com secure website, which will then allocate the appropriate trial identification code to the patient…… All patients will be randomly assigned to treatment via the SealedEnvelope.com website"
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"SealedEnvelope will provide the patient trial identification codes at randomisation. The trial drug kit identification code list will be prepared by the Trial Statistician and provided separately to SealedEnvelope and to the QP, who will ensure that labelling of trial drug packs occurs appropriately and so as to ensure complete blinding of the IMP to all investigators, participants, and the pharmacy staff on the study"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Triple blinding of investigators, participants, and pharmacy staff "To prevent the possibility of adverse events compromising rater blinding, all adverse events, biochemical results, blood pressure, heart rate, and weight were recorded separately by clinicians who were masked to treatment allocation"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Attrition rate was low (< 5%) and balanced between groups
Selective reporting (reporting bias)	Low risk	None was identified
Other bias	Low risk	None was identified. Some baseline imbalances were noted (i.e. MDS‐UPDRS scores); however, these were adjusted for in the data analysis