Efficacy and safety of glucagon-like peptide 1 agonists for Parkinson's disease: a systematic review and meta-analysis.

Background:  Recent research on Parkinson's disease (PD) therapy has highlighted glucagon-like peptide 1 (GLP-1) agonists as potential therapeutic agents. However, recent randomized controlled trials (RCTs) have shown mixed results regarding the use of this medication.

Objective:  To perform a meta-analysis comparing GLP-1 agonists with placebo or standard PD treatment in adult PD patients.

Methods:  We systematically searched the PubMed, Embase and Cochrane Central databases. The efficacy outcomes were assessed through the Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) and the 39-item Parkinson's Disease Questionnaire (PDQ-39). We also assessed adverse events. Dichotomous data were compared using the risk ratio (RR), and continuous endpoints were pooled using the mean difference (MD).

Results:  We included 4 RCTs, with a total of 514 patients. In every study, the Hoehn and Yahr stage was < 3. The pooled analysis demonstrated that the use of GLP-1 agonists was not associated with an improvement in the scores on parts I, II, III, and IV of the MDS-UPDRS at 6 and 12 months of follow-up. Neither did quality of life (PDQ-39) show significant differences among the groups, and a higher risk of gastrointestinal adverse events and weight loss was observed with the use of GLP-1 agonists. A subgroup analysis further confirmed the lack of clinical benefits of the intervention regarding all of these efficacy outcomes, and the intervention also significantly reduced result heterogeneity.

Conclusions:  In 1 year, GLP-1 agonists failed to improve motor and non-motor features of PD. Additional high-quality studies are needed to draw more robust conclusions about this treatment.