The effect of GLP-1 receptor agonists on anxiety: A systematic review

Anxiety-like behaviors are highly prevalent and frequently co-occur with metabolic conditions such as type 2 diabetes and obesity, suggesting the potential for shared biological mechanisms. Although glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for glycemic control and weight management, emerging evidence indicates that they may also influence neuroinflammation, neuroplasticity, and affective regulation. However, findings across preclinical and clinical studies remain fragmented, and no systematic synthesis has directly evaluated their effects on anxiety-like behaviors. This review addresses this gap by examining whether GLP-1 RA administration reduces anxiety-like behaviors or clinically coded anxiety outcomes. Following PRISMA guidelines, preclinical and clinical studies were systematically identified, screened using PICOS-defined criteria, and evaluated with validated quality assessment tools. Across animal studies, GLP-1 RAs consistently reduced anxiety-like behaviors and improved neurobiological markers related to stress resilience, while clinical cohorts demonstrated mixed but suggestive evidence of reduced anxiety incidence and lower suicidal ideation risk. These findings highlight the potential for GLP-1 RAs to modulate both metabolic and psychiatric pathways, underscoring the need for randomized controlled trials to clarify causal effects and inform their role in metabolic psychiatry.