Targeting Metabolic Dysfunction in Parkinson's Disease: The Role of GLP-1 Agonists in Body Weight Regulation and Neuroprotection.

PURPOSE OF REVIEW: This review explores the role of GLP-1 receptor agonists (GLP-1 RAs) in addressing metabolic dysfunction and neurodegeneration in Parkinson's disease (PD), focusing on body weight regulation and neuroprotection.

RECENT FINDINGS: GLP-1 RAs modulate insulin signaling, reduce neuroinflammation and oxidative stress, and improve mitochondrial functional mechanisms linked to neuroprotection. Clinical trials show modest but sustained improvements in motor symptoms and suggest benefits in cognition, mood, and apathy. While GLP-1 RAs induce weight loss in diabetes, their metabolic impact in normoglycaemic PD patients appears limited. However, individuals with obesity or insulin resistance may experience enhanced clinical and cognitive outcomes. GLP-1 RAs offer a multifaceted therapeutic strategy in PD, targeting both central neurodegenerative processes and peripheral metabolic dysfunction. Their potential for disease modification and symptom relief, particularly in specific phenotypes, supports their further exploration as part of a personalized treatment approach.