Semaglutide's Role in Modulating the Brain-Heart Axis: Implications for Obesity and Alzheimer’s Disease Co-management

Purpose: This study aimed to investigate the potential of Semaglutide, a GLP-1 receptor agonist, in modulating the brain-heart axis and offering a dual-therapeutic benefit for patients with comorbid obesity and Alzheimer’s disease. Methodology: A comprehensive review of recent clinical trials, experimental studies, and mechanistic analyses published between 2020 and 2025 was conducted using data sourced from PubMed, Scopus, and Embase. The inclusion criteria focused on studies exploring Semaglutide's effects on neuroinflammation, cardiovascular function, cognition, and metabolic parameters. Both qualitative synthesis and quantitative meta-analyses were applied. Additional data visualization techniques were employed to present key findings through tables, charts, and pathway diagrams. Findings: The analysis revealed that Semaglutide reduced key pro-inflammatory biomarkers (e.g., IL-6, TNF-α), improved heart rate variability, and showed neuroprotective effects by enhancing cerebral blood flow and preserving cognitive function in early-stage AD patients. Clinically, Semaglutide led to substantial weight loss, improved glycemic control, and favorable cardiovascular outcomes. Meta-analytic data showed statistically significant improvements in cognitive assessments (MMSE and MoCA scores) and cardiometabolic markers in dual-diagnosis patients, indicating the agent’s cross-system therapeutic relevance. Unique Contribution to Theory, Policy, and Practice: This study provides a novel framework for understanding the role of GLP-1 receptor agonists in modulating the brain-heart axis and managing dual-pathology in metabolic and neurodegenerative diseases. It offers translational insights for clinicians seeking integrated treatment strategies and emphasizes the importance of repositioning Semaglutide as a potential therapeutic candidate beyond diabetes and obesity, particularly in neurocardiometabolic comorbidity management. Future policy and clinical trials should focus on long-term safety, patient stratification, and the incorporation of brain-heart biomarkers into therapeutic decision-making.