Antidiabetic Agents as Antioxidant and Anti-Inflammatory Therapies in Neurological and Cardiovascular Diseases

Neurological disorders and cardiovascular disease (CVD) remain leading causes of global morbidity and mortality and often coexist, in part through shared mechanisms of chronic inflammation and oxidative stress. Neuroinflammatory signaling, including microglial activation, cytokine release, and impaired autonomic regulation, contributes to endothelial dysfunction, atherosclerosis, hypertension, and stroke, while cardiac and metabolic disturbances can reciprocally exacerbate brain pathology. Increasing evidence shows that several antidiabetic agents exert pleiotropic anti-inflammatory and antioxidant effects that extend beyond glycemic control. Metformin, SGLT2 inhibitors, DPP-4 inhibitors, and GLP-1 receptor agonists modulate key pathways such as AMPK, NF-κB, Nrf2 activation, and NLRP3 inflammasome suppression, with demonstrated vascular and neuroprotective actions in preclinical models. Clinically, GLP-1 receptor agonists and SGLT2 inhibitors reduce major cardiovascular events, improve systemic inflammatory markers, and show emerging signals for cognitive benefit, while metformin and DPP-4 inhibitors exhibit supportive but less robust evidence. This review synthesizes molecular, preclinical, and clinical data across drug classes, with particular emphasis on GLP-1 receptor agonists, and highlights outstanding translational questions including blood-brain barrier penetration, biomarker development, optimal patient selection, and timing of intervention. We propose a unified framework to guide future trials aimed at leveraging antidiabetic therapies such as DDP-4 anti-inflammatory and antioxidant interventions for neurological and cardiovascular diseases.