The Impact of Sodium Glucose Co-Transporter 2 (SGLT-2) Inhibitors on Atherogenesis: A Systematic Review of Experimental and Clinical Evidence

<b>Background:</b> Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated significant benefits in cardiovascular outcomes trials, but their effect on atherosclerotic plaques remains unclear. This review aims to summarize the current evidence on the impact of SGLT2i on atherogenesis. <b>Methods:</b> A systematic search was conducted across PubMed, Embase, Scopus, Web of Science, and Google Scholar databases up to August 2025. Preclinical and clinical studies on the effect of SGLT2i on atherogenesis and atherosclerotic plaque extent and phenotype were included. <b>Results:</b> A total of 27 studies were included. Twenty-four studies examined in vitro and animal models of atherosclerosis exposed to SGLT2i, while three studies focused on the effects of SGLT2i on coronary plaques in patients with ischemic heart disease. SGLT2is modulate atherogenesis through multiple mechanisms: prevention and reversal of endothelial dysfunction, reduction in monocyte recruitment and promotion of anti-inflammatory macrophage polarization. Additionally, SGLT2is reduce inflammation and inhibit vascular calcification. Through these mechanisms, SGLT2is decrease plaque burden in both diabetic and non-diabetic atherosclerosis models. Furthermore, they reduce lipid content and macrophages accumulation while increasing fibrous cap thickness, thereby contributing to plaque stabilization. <b>Conclusions:</b> Preclinical and clinical evidence suggest that SGLT2is modulate every step of the atherogenic process, reduce atherosclerotic burden and promote coronary plaque stabilization.