Beyond Diabetes Mellitus and weight loss: the potential effect of GLP-1 agonist drugs in the treatment of Parkinson’s Disease

Introduction Drugs targeting insulin resistance in the brain have emerged as a potential therapeutic option for Parkinson's disease (PD). Their implication has originated from the studies indicating a link between Type 2 Diabetes Mellitus (T2DM) and PD, indicating that impairment in glucose and energy metabolism pathways contribute to the pathogenesis of PD. Owing to their potential neuroprotective properties in PD, glucagon-like peptide-1 (GLP-1) receptor agonists represent a category of antidiabetic medications that have garnered interest.  The aim of this review is to evaluate the role of GLP-1 agonists as a novel treatment option for Parkinson’s disease concentrating on disease modifying effects. Methods The search of literature was performed in databases including PubMed, Google Scholar and ScienceDirect, the timeline applied was from years 2017 to 2025. Keywords used were “Parkinson's disease”, “glucagon-like peptide”, “glp-1 agonists”, “semaglutide”. Priority was set to peer-reviewed research, preclinical studies and clinical trials. References were screened for additional studies that could support the evidence. Results Data from preclinical and animal studies show, that GLP-1 agonists could modify the main pathological pathways impaired in Parkinson’s disease, including energy metabolism and neuroprotection. They improved the cell survival rate, autophagy stimulation, and reduced the apoptosis of mitochondria in cytotoxic in vitro cell models of PD and reduced the levels of alpha-synuclein in the brain in the mice models. Similarly, in rat model studies, incretin mimetics reduced pro-inflammatory cytokine levels, including TNFα, NF-kB and cyclooxygenase (COX1) and were able to regulate the function of microglial cells. GLP-1 agonists could improve dopaminergic transmission - they were shown to promote dopaminergic cell viability in substantia nigra pars compacta and normalize the tyrosine hydroxylase expression. Treatment with GLP-1 agonists have a positive impact on clinical features of PD. Marked improvement of motor function was seen as a result in the clinical trials, expressed by increase in MDS-UPDRS part III scales, as well as non-motor symptoms including cognition, mood and activities of daily living. Conclusions GLP-1 agonists show promise to have a disease modifying effect in Parkinson’s Disease by targeting factors like inflammation, insulin resistance, aiding in neuroprotection and improving motor and non-motor symptoms. As the existing knowledge gap renders making possible conclusions about the efficacy of these drugs in PD populations without insulin resistance and inflammation rather difficult, further research and clinical trials should be conducted to confirm or deny the same.