Abstract
Selective sodium–glucose cotransporter 2 (SGLT2) inhibitors reduced the risk of hospitalization for heart failure in patients with or without type 2 diabetes (T2DM) in large-scale clinical trials. The exact mechanism of action is currently unclear. The dual SGLT1/2 inhibitor sotagliflozin not only reduced hospitalization for HF in patients with T2DM, but also lowered the risk of myocardial infarction and stroke, suggesting a possible additional benefit related to SGLT1 inhibition. In fact, several preclinical studies suggest that SGLT1 plays an important role in cardiac pathophysiological processes. In this review, our aim is to establish the clinical significance of myocardial SGLT1 inhibition through reviewing basic research studies in the context of SGLT2 inhibitor trials.
Highlights
As the incidence of type 2 diabetes mellitus (T2DM) is steadily increasing [1], sodium–glucose cotransporter 2 (SGLT2) inhibitors have been developed as a novel class of antihyperglycemic agents
Several studies documented that humans with heart failure (HF) exhibit increased LV SGLT1 mRNA or protein expression as compared with non-failing controls, including those with dilated cardiomyopathy (DCM) [41], ischemic cardiomyopathy (ICM) [39,41,51], hypertrophic cardiomyopathy (HCM) [39], and those with T2DM [41,51,54], or mixed cohorts of these HF etiologies [54]
Some studies found no significant difference in LV SGLT1 expression in patients with HCM [41], or DCM [40,51], or ICM [40] compared with nonfailing controls
Summary
As the incidence of type 2 diabetes mellitus (T2DM) is steadily increasing [1], sodium–. Several large cardiovascular outcome trials in high-risk T2DM patients have been conducted with selective SGLT2 inhibitors [2,3,4,5,6] and one with the dual SGLT1/2 inhibitor sotagliflozin [7]. These medications have proven to be safe, but they have shown robust salutary cardiorenal protection as a class effect, with currently unclear mechanism of action. Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations
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