The Role of SGLT2 Inhibitors in Atherosclerosis: A Systematic Review.

Background: Atherosclerosis, a major cause of cardiovascular morbidity and mortality, involves lipid accumulation, endothelial dysfunction, inflammation, and oxidative stress. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, initially developed for type 2 diabetes mellitus (T2DM), have demonstrated cardiovascular benefits beyond glycemic control. Emerging evidence suggests their potential role in slowing atherosclerosis progression and enhancing plaque stability. Methods: A systematic review of PubMed, Scopus, Embase, and Cochrane Library databases was conducted to identify preclinical and clinical studies on SGLT2 inhibitors and atherosclerosis. Studies published in English up to December 2024 were screened using predefined criteria. Data on mechanisms, lipid metabolism, endothelial function, vascular inflammation, and plaque stability were extracted, and study quality was assessed. Results: A total of 16 animal and 4 human studies were included. SGLT2 inhibitors (empagliflozin, dapagliflozin, and canagliflozin) improved glycemic control, lipid metabolism, and atheroma reduction while enhancing plaque stability. They modestly reduced triglycerides and LDL-C while increasing HDL-C. SGLT2 inhibitors also decreased vascular inflammation and enhanced plaque stability by increasing fibrous cap thickness. Cardiovascular outcome trials demonstrated reductions in major adverse cardiovascular events (MACE) and heart failure hospitalizations, indirectly supporting their atheroprotective role. Conclusion: SGLT2 inhibitors offer a multifaceted approach to atherosclerosis management by improving lipid metabolism, endothelial function, vascular inflammation, and plaque stability. While evidence is promising, further research is needed to confirm direct anti-atherosclerotic effects, optimize their role in cardiovascular care.