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Volume 15
Issue 11
10.3390/life15111784
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Systematic Review

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

by
Filippo Luca Gurgoglione
1,†,
Marco Covani
1,†,
Laura Torlai Triglia
1,
Giorgio Benatti
1,
Davide Donelli
1,
Michele Bianconcini
1,
Emilia Solinas
1,
Iacopo Tadonio
1,
Andrea Denegri
1,
Mattia De Gregorio
1,
Gabriella Dallaglio
1,
Alessandra Dei Cas
2,3,
Riccardo C. Bonadonna
3,4,5,
Luigi Vignali
1,3 and
Giampaolo Niccoli
1,3,*
1
Division of Cardiology, Parma University Hospital, University of Parma, 43126 Parma, Italy
2
Department of Endocrinology and Metabolic Diseases, Parma University Hospital, 43126 Parma, Italy
3
Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
4
Department of Endocrinology, Diabetology and Metabolic Diseases, University of Verona, 37134 Verona, Italy
5
Department of Medicine and Surgery, University Hospital of Verona, 37134 Verona, Italy
*
Author to whom correspondence should be addressed.
†
These authors equally contributed as first author.
Life 2025, 15(11), 1784; https://doi.org/10.3390/life15111784 (registering DOI)
Submission received: 24 October 2025 / Revised: 16 November 2025 / Accepted: 20 November 2025 / Published: 20 November 2025
(This article belongs to the Section Medical Research)
Versions Notes

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: Preclinical and clinical evidence suggest that SGLT2is modulate every step of the atherogenic process, reduce atherosclerotic burden and promote coronary plaque stabilization.
Keywords: diabetes mellitus; coronary artery disease; sodium-glucose cotransporter-2 inhibitors; atherogenesis; inflammation; plaque regression; plaque stability diabetes mellitus; coronary artery disease; sodium-glucose cotransporter-2 inhibitors; atherogenesis; inflammation; plaque regression; plaque stability

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MDPI and ACS Style

Gurgoglione, F.L.; Covani, M.; Torlai Triglia, L.; Benatti, G.; Donelli, D.; Bianconcini, M.; Solinas, E.; Tadonio, I.; Denegri, A.; De Gregorio, M.; et al. The Impact of Sodium Glucose Co-Transporter 2 (SGLT-2) Inhibitors on Atherogenesis: A Systematic Review of Experimental and Clinical Evidence. Life 2025, 15, 1784. https://doi.org/10.3390/life15111784

AMA Style

Gurgoglione FL, Covani M, Torlai Triglia L, Benatti G, Donelli D, Bianconcini M, Solinas E, Tadonio I, Denegri A, De Gregorio M, et al. The Impact of Sodium Glucose Co-Transporter 2 (SGLT-2) Inhibitors on Atherogenesis: A Systematic Review of Experimental and Clinical Evidence. Life. 2025; 15(11):1784. https://doi.org/10.3390/life15111784

Chicago/Turabian Style

Gurgoglione, Filippo Luca, Marco Covani, Laura Torlai Triglia, Giorgio Benatti, Davide Donelli, Michele Bianconcini, Emilia Solinas, Iacopo Tadonio, Andrea Denegri, Mattia De Gregorio, and et al. 2025. "The Impact of Sodium Glucose Co-Transporter 2 (SGLT-2) Inhibitors on Atherogenesis: A Systematic Review of Experimental and Clinical Evidence" Life 15, no. 11: 1784. https://doi.org/10.3390/life15111784

APA Style

Gurgoglione, F. L., Covani, M., Torlai Triglia, L., Benatti, G., Donelli, D., Bianconcini, M., Solinas, E., Tadonio, I., Denegri, A., De Gregorio, M., Dallaglio, G., Dei Cas, A., Bonadonna, R. C., Vignali, L., & Niccoli, G. (2025). The Impact of Sodium Glucose Co-Transporter 2 (SGLT-2) Inhibitors on Atherogenesis: A Systematic Review of Experimental and Clinical Evidence. Life, 15(11), 1784. https://doi.org/10.3390/life15111784

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