Cardioprotective Mechanisms of Metformin: A Review of Molecular Pathways and Therapeutic Implications Beyond Glycemic Control
Youssef, M., Shehtou, G., Abdelkader, E., EL-Abasy, H. (2025). Cardioprotective Mechanisms of Metformin: A Review of Molecular Pathways and Therapeutic Implications Beyond Glycemic Control. EKB Journal Management System, 8(1), 32-39. doi: 10.21608/dusj.2025.356991.1120
Mahmoud E Youssef; George Shehtou; Eman Abdelkader; Hamsa EL-Abasy. "Cardioprotective Mechanisms of Metformin: A Review of Molecular Pathways and Therapeutic Implications Beyond Glycemic Control". EKB Journal Management System, 8, 1, 2025, 32-39. doi: 10.21608/dusj.2025.356991.1120
Youssef, M., Shehtou, G., Abdelkader, E., EL-Abasy, H. (2025). 'Cardioprotective Mechanisms of Metformin: A Review of Molecular Pathways and Therapeutic Implications Beyond Glycemic Control', EKB Journal Management System, 8(1), pp. 32-39. doi: 10.21608/dusj.2025.356991.1120
Youssef, M., Shehtou, G., Abdelkader, E., EL-Abasy, H. Cardioprotective Mechanisms of Metformin: A Review of Molecular Pathways and Therapeutic Implications Beyond Glycemic Control. EKB Journal Management System, 2025; 8(1): 32-39. doi: 10.21608/dusj.2025.356991.1120

Cardioprotective Mechanisms of Metformin: A Review of Molecular Pathways and Therapeutic Implications Beyond Glycemic Control

Delta University Scientific Journal
Volume 8, Issue 1, April 2025, Page 32-39  XML PDF (273.15 K)
Document Type: Review articles
DOI: 10.21608/dusj.2025.356991.1120
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Authors
Mahmoud E Youssef email 1; George Shehtou2; Eman Abdelkader2; Hamsa EL-Abasy2
1Faculty of Pharmacy, Delta University for Science and Technology.
2Department of Pharmacology and Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, International Coastal Road, Gamasa, Dakahliya, Egypt
Abstract
Metformin (MET), a cornerstone therapy for type 2 diabetes, exhibits multifaceted therapeutic benefits extending beyond its hypoglycemic effects. This review synthesizes recent research on MET’s cardioprotective mechanisms, emphasizing its modulation of critical molecular pathways. MET activates AMP-activated protein kinase (AMPK), a central energy sensor that enhances fatty acid oxidation, suppresses hepatic gluconeogenesis, and mitigates cardiac dysfunction via anti-inflammatory, anti-apoptotic, and autophagy-regulating actions. Additionally, MET inhibits the Nuclear Factor Kappa B (NF-κB) pathway, reducing pro-inflammatory cytokine production (e.g., TNF-α, IL-6, IL-1β) and attenuating endothelial dysfunction. Its suppression of the NLRP3 inflammasome further curtails oxidative stress and inflammation, pivotal contributors to diabetic cardiomyopathy and atherosclerosis. Pharmacokinetic insights underscore MET’s renal clearance and safety profile, while its inhibition of mitochondrial complex I reduces reactive oxygen species (ROS), bolstering antioxidant defenses. Collectively, MET’s pleiotropic effects—mediated through AMPK, NF-κB, NLRP3, and oxidative stress pathways—highlight its potential as a therapeutic agent for cardiovascular diseases. This review underscores the need for further clinical exploration of MET’s repurposing in cardiometabolic disorders, leveraging its molecular mechanisms to optimize patient outcomes beyond diabetes management
Keywords
Metformin; inflammation; NF-kB; NLRP3; Cytokines
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