GLP-1 receptor agonists for Parkinson's disease

• Published in: Cochrane database of systematic reviews 2020-07, Vol.7 (7), p.CD012990
• Main Authors: Mulvaney, Caroline A, Duarte, Gonçalo S, Handley, Joel, Evans, David Jw, Menon, Suresh, Wyse, Richard, Emsley, Hedley Ca
• Format: Article
• Language: English
• Subjects: Akinetic-rigid syndrome; Bias; Double-Blind Method; Exenatide - administration & dosage; Exenatide - adverse effects; Exenatide - therapeutic use; Glucagon-Like Peptide-1 Receptor - agonists; Humans; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - therapeutic use; Neurology; Parkinson Disease - drug therapy; Placebos - administration & dosage; Quality of Life; Randomized Controlled Trials as Topic; Self Administration; Single-Blind Method
• ISSN: 1469-493X; 1469-493X
• DOI: 10.1002/14651858.CD012990.pub2

Parkinson's disease (PD) is a progressive disorder characterised by both motor and non-motor problems. Glucagon-like peptide-1 (GLP-1) receptor agonists, licensed for treatment of type 2 diabetes, work by stimulating GLP-1 receptors in the pancreas, which triggers the release of insulin. GLP-1 receptors have been found in the brain. Insulin signalling in the brain plays a key role in neuronal metabolism and repair and in synaptic efficacy, but insulin signalling is desensitised in the brain of people with PD. Researchers are exploring the neuroprotective effects of GLP-1 receptor agonists in neurodegenerative disorders such as PD. To evaluate the effectiveness and safety of GLP-1 receptor agonists for Parkinson's disease. We searched the Cochrane Movement Disorders Group trials register; the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; and Ovid MEDLINE and Embase. We also searched clinical trials registries, and we handsearched conference abstracts. The most recent search was run on 25 June 2020. We included randomised controlled trials (RCTs) of adults with PD that compared GLP-1 receptor agonists with conventional PD treatment, placebo, or no treatment. Two review authors independently assessed studies for inclusion, extracted data, and assessed risk of bias. We rated the quality of evidence using GRADE. We resolved discrepancies between the two data extractors by consultation with a third review author. Through our searches, we retrieved 99 unique records, of which two met our inclusion criteria. One double-blind study of exenatide versus placebo randomised 62 participants, who self-administered exenatide or placebo for 48 weeks and were followed up at 60 weeks after a 12-week washout. One single-blind study of exenatide versus no additional treatment randomised 45 participants; participants in the intervention group self-administered exenatide for 12 months, and all participants were followed up at 14 months and 24 months following absence of exenatide for 2 months and 12 months, respectively. These trials had low risk of bias, except risk of performance bias was high for Aviles-Olmos 2013. Exenatide versus placebo Primary outcomes We found low-certainty evidence suggesting that exenatide improves motor impairment as assessed by the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III in the off-medication state (mean difference (MD) -3.10, 95% confidence interval (CI) -6.11 to -0