Efficacy and Safety of Glucagon-Like Peptide 1 Receptor Agonists in Parkinson Disease: A Systematic Review and Meta-Analysis.
A recent systematic review and meta-analysis evaluated the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) for Parkinson's disease (PD). This research is crucial given that PD currently lacks approved disease-modifying treatments.
Brain Behav
by Raza H, Nizam B, Padaniya A et al.
“Efficacy and Safety of Glucagon-Like Peptide 1 Receptor Agonists in Parkinson Disease: A Systematic Review and Meta-Analysis. Raza H(1), Nizam B(2), Padaniya A(3), Farid MA(4), Nabi A(5), Hasan MQ(6), Salih M(7), Patel AH(8), Inam N(9), Rehman MEU(10), Khan U(11), Alsubari AMA(12). Author information: (1)Department of Medicine, Lahore Medical and Dental College, Lahore, Pakistan. (2)Department of Medicine, Women Medical College, Abbotabad, Pakistan. (3)Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio, USA. (4)Department of Geriatrics, Oxleas NHS Trust, London, UK. (5)Department of Medicine, Ziauddin University, Karachi, Pakistan. (6)Department of Medicine, Allama Iqbal Medical College, Lahore, Pakistan. (7)Department of Medicine, Dow University Hospital, Karachi, Pakistan. (8)Department of Neurology, Medical University of South Carolina, Charleston, South Carolina, USA. (9)Department of Medicine, Gajju Khan Medical College, Swabi, Pakistan. (10)Department of Medicine, Rawalpindi Medical University, Rawalpindi, Pakistan. (11)Department of Neurology, Geisinger Hospital, Scranton, Pennsylvania, USA. (12)Department of Medicine, Sana'a University, Sana'a, Yemen. BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder with no currently approved disease-modifying treatments. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), originally used in type 2 diabetes, have demonstrated neuroprotective and anti-inflammatory effects in preclinical PD models. This systematic review and meta-analysis evaluated the efficacy and safety of GLP-1RAs in patients with PD. METHODS: A systematic search of MEDLINE, Embase, Cochrane CENTRAL, and ClinicalTrials.gov was conducted through July 2025 for randomized controlled trials (RCTs) comparing GLP-1RAs to placebo in PD. Primary outcomes included MDS-UPDRS Part III (motor examination) both on and off medication. Secondary outcomes included MDS-UPDRS Parts I, II, IV, PDQ-39, NMSS, and adverse effects. Data were pooled using a random-effects model with results reported as mean differences (MD) or risk ratios (RR) with 95% confidence intervals (CI). RESULTS: Five RCTs involving 708 participants were included. No statistically significant differences were found in MDS-UPDRS Part III scores off medication (MD: -2.00, 95% CI: -4.12 to 0.11, p = 0.06) or on medication (MD: -1.40, 95% CI: -3.42 to 0.62, p = 0.17). Secondary outcomes also showed no significant benefits with GLP-1RA use. However, GLP-1RAs were associated with increased gastrointestinal side effects, including nausea (RR: 2.09), vomiting (RR: 4.53), constipation (RR: 1.60), and weight loss (RR: 1.83). CONCLUSION: Current evidence does not demonstrate a statistically significant overall benefit of GLP-1RAs on efficacy outcomes in PD, while gastrointestinal adverse events are increased. More trials are needed to clarify their disease-modifying potential. © 2026 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.”
Researchers scoured databases like MEDLINE and Cochrane CENTRAL for randomized controlled trials comparing GLP-1RAs to placebo in PD patients. They focused on primary outcomes such as motor function scores and various secondary assessments related to quality of life and adverse effects.
Here’s what they found:
Five trials with 708 participants were included in the analysis.
No significant improvements were observed in motor scores, whether patients were on or off medication.
Secondary outcomes also showed no notable benefits from GLP-1RAs.
There was an uptick in gastrointestinal side effects:
Nausea (risk ratio: 2.09)
Vomiting (risk ratio: 4.53)
Constipation (risk ratio: 1.60)
Weight loss (risk ratio: 1.83)
While the study concluded that GLP-1RAs did not yield statistically significant benefits for PD patients, the increased side effects warrant attention. The findings suggest a need for further research to explore the potential of GLP-1RAs in modifying the disease.
This is a solid step in understanding how these research peptides interact with neurodegenerative conditions. Continued investigation could open new avenues for treatment in Parkinson's disease.
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