The effect of GLP-1 receptor agonists in pre-clinical rodent models of Parkinson’s disease: A systematic review and meta-analysis

BACKGROUND: Parkinson’s Disease (PD) is a progressive neurodegenerative condition associated with significant morbidity. Currently, there are limited pharmacological options and none of the therapies available are disease-modifying. This systematic review and meta-analysis considers a novel drug class through the research question – in pre-clinical rodent models of PD, is GLP-1 receptor agonist therapy neuroprotective when compared to vehicle controls? METHODS: A literature search was conducted to locate relevant pre-clinical studies. Two separate outcomes were considered. The primary outcome was indicators of dopaminergic neurotransmission. The secondary outcome was indicators of motor symptoms. Untreated PD models were compared to PD-models treated with GLP-1 receptor agonists. The final meta-analysis was conducted using the Cochrane RevMan software and represented continuous data using the inverse variance statistical method and random effects analysis model. The final study statistic was represented as an SMD value with a p-value < 0.05 considered statistically significant. Study heterogeneity and publication bias was assessed using I(2) values and funnel plots respectively. RESULTS: Eleven studies fit the inclusion criteria and were included in the final analysis. For the primary outcome (n = 128), there was a statistically significant relative improvement of dopaminergic neurotransmission (SMD 1.71, 95% CI = 0.74–2.68, p = 0.0005, I(2) = 76%). For the secondary outcome (n = 280), there was a statistically significant improvement in motor outcomes (SMD 2.11, 95% CI = 1.14–3.09, p < 0.0001, I(2) = 89%). CONCLUSIONS: GLP-1 receptor agonist therapy is neuroprotective in pre-clinical models of PD. This study provides the clinical foundation and research support for the design of rigorous clinical trials to further investigate these results in human PD populations.