Abstract
Sodium glucose cotransporter 2 (SGLT2) inhibitors are a class of medication with broad cardiovascular benefits in those with type 2 diabetes, chronic kidney disease, and heart failure. These include reductions in major adverse cardiac events and cardiovascular death. The mechanisms that underlie their benefits in atherosclerotic cardiovascular disease (ASCVD) are not well understood, but they extend beyond glucose lowering. This narrative review summarises the ASCVD benefits of SGLT2 inhibitors seen in large human outcome trials, as well as the mechanisms of action explored in rodent and small human studies. Potential pathways include favourable alterations in lipid metabolism, inflammation, and endothelial function. These all require further investigation in large human clinical trials with mechanistic endpoints, to further elucidate the disease modifying benefits of this drug class and those who will benefit most from it.
Highlights
Sodium glucose cotransporter 2 (SGLT2) inhibitors are a class of medication that act in the proximal nephron to reduce glucose reabsorption, thereby causing glycosuria and modest reductions in blood sugar levels
In DAPACKD [9], SGLT2 inhibition results in a 19% reduction in CV mortality (HR 0.81, 95% CI 0.58 to 1.12) and in the heart failure population DAPA-HF [10] demonstrated a CV
Significant reductions in body weight, blood pressure, albuminuria, and glycosylated haemoglobin (HbA1C) were observed [1,2,3,4]. This offers a potential mechanism by which SGLT2 inhibitors could be mediating an atherosclerotic cardiovascular disease (ASCVD) benefit in treated individuals
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. A possible signal of reduction in stroke in those with reduced kidney function identified in a recent meta-analysis has raised additional questions about how the drug class might be effecting mechanisms of atherosclerosis [5]. This narrative review consolidates the available literature from animal and human studies describing the major clinical outcomes of SGLT2 inhibition in ASCVD and explores the potential mechanisms underpinning these effects with key findings presented
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