The Role of SGLT2 Inhibitors in Atherosclerosis: A Narrative Mini-Review

Aurélie Pahud de Mortanges; Dante Salvador Jr; Markus Laimer; Taulant Muka; Matthias Wilhelm; Arjola Bano

doi:10.3389/fphar.2021.751214

The Role of SGLT2 Inhibitors in Atherosclerosis: A Narrative Mini-Review

Front Pharmacol. 2021 Nov 5:12:751214. doi: 10.3389/fphar.2021.751214. eCollection 2021.

Authors

Aurélie Pahud de Mortanges¹, Dante Salvador Jr^{2

3}, Markus Laimer⁴, Taulant Muka², Matthias Wilhelm³, Arjola Bano^{2

3}

Affiliations

¹ Faculty of Medicine, University of Bern, Bern, Switzerland.
² Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
³ Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
⁴ Department of Diabetes, Endocrinology, Nutritional Medicine, and Metabolism, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

Abstract

Objective: Sodium glucose cotransporter 2 inhibitors (SGLT2-is) are antidiabetic drugs that improve glycemic control by limiting urinary glucose reuptake in the proximal tubule. SGLT2-is might suppress atherosclerotic processes and ameliorate the prognosis of patients with diabetes mellitus diagnosed with or at high risk of atherosclerotic cardiovascular disease (ASCVD). In this mini review, we examine the role of SGLT2-is in the development and progression of atherosclerosis throughout its spectrum, from subclinical atherosclerosis to ASCVD. Data Sources-PubMed and Google Scholar were searched for publications related to SGLT2-is and atherosclerosis. All types of articles were considered, including clinical trials, animal studies, in vitro observations, and reviews and meta-analyses. Data were examined according to their impact and clinical relevance. Synopsis of Content-We first review the underlying mechanisms of SGLT2-is on the development and progression of atherosclerosis, including favorable effects on lipid metabolism, reduction of systemic inflammation, and improvement of endothelial function. We then discuss the putative impact of SGLT2-is on the formation, composition, and stability of atherosclerotic plaque. Furthermore, we evaluate the effects of SGLT2-is in subclinical atherosclerosis assessed by carotid intima media thickness and pulse wave velocity. Subsequently, we summarize the effects of SGLT2-is in ASCVD events, including ischemic stroke, angina pectoris, myocardial infarction, revascularization, and peripheral artery disease, as well as major adverse cardiovascular events, cardiovascular mortality, heart failure, and chronic kidney disease. Moreover, we examine factors that could modify the role of SGLT2-is in atherosclerosis, including sex, age, diabetes, glycemic control, ASCVD, and SGLT2-i compounds. Additionally, we propose future directions that can improve our understanding of SGLT2-is and atherosclerosis.

Keywords: SGLT2-inhibitors; atherosclerotic cardiovascular disease; diabetes; review; subclinical atherosclerosis.

Publication types

Review