Safety and efficacy of glucagon-like peptide 1 receptor agonists for Parkinson's disease: a meta-analysis of randomized controlled trials

Background: Parkinson's disease (PD) affects 6.1 million people worldwide. Oral treatments like l-DOPA may not be ideal for Parkinson's patients with dysphagia and can aggravate non-motor symptoms over time. Glucagon-like peptide 1 (GLP-1) receptors in the brain and an association between insulin resistance and PD suggest GLP-1 agonists as a promising alternative for these patients. This systematic review and meta-analysis evaluate the safety and efficacy of GLP-1 receptor agonists in improving motor and non-motor symptoms in PD. Methods: PubMed, Cochrane, and Clinicaltrials.gov were searched systematically up to 01/05/2024 for randomized controlled trials (RCTs) on GLP-1 receptor agonists' efficacy in PD. Results: Quantitative analysis of five studies with 480 patients showed no significant difference between the intervention and the control groups for Movement Disorder Society-Sponsored Unified Parkinson's Disease Rating Scale part I (standard mean deviation (SMD): -0.11; 95% CI: -0.29, 0.07, P = 0.23), part II (SMD: -0.16; 95% CI: -0.43, 0.11, P = 0.25), part IV (SMD: -0.18; 95% CI: -0.46, 0.10, P = 0.20), diarrhea (RR: 1.28; 95% CI: 0.80, 2.07, P = 0.30), urinary tract infection (RR: 0.92; 95% CI: 0.34, 2.50, P = 0.87), back pain (RR: 0.76; 95% CI: 0.38, 1.52, P = 0.30), anxiety (RR: 1.62; 95% CI: 0.44, 6.00, P = 0.47), and injection site reaction (RR: 1.10; 95% CI: 0.74, 1.63, P = 0.65). However, there was a significant improvement in part III (SMD: -0.20; 95% CI: -0.39, -0.01, P = 0.04), and a statistically significant risk of nausea (RR: 2.31; 95% CI: 1.59, 3.36, P < 0.0001), weight loss (RR: 3.21; 95% CI: 2.00, 5.17, P = 0.02), vomiting (RR: 4.77; 95% CI: 1.66, 13.68, P = 0.004), and constipation (RR: 1.44; 95% CI: 1.07, 1.95, P = 0.02) in the intervention group compared to the control group. Conclusion: GLP-1 receptor agonists may improve motor symptoms but are not safe and effective in improving non-motor symptoms in PD patients.