SGLT2 transcriptomic expression atlas supports a kidney-centric role for empagliflozin's benefits in heart failure

Abstract

Sodium-glucose cotransporter 2 inhibitors (SGLT2i), such as empagliflozin, have shown remarkable benefits in reducing cardiovascular events and mortality in patients with heart failure (HF) irrespective of diabetic status. Because of the magnitude of the benefits and broad application in both HF with reduced and preserved ejection fraction (EF), there have been concerted efforts to identify a mechanism for the observed benefits. One hypothesis is that SGLT2i act directly on the heart. Given empagliflozins high specificity to SGLT2, we reasoned that SGLT2 expression would be a requirement for cells to respond to treatment. Here, we present a comprehensive transcriptomic analysis of SLC5A2, which encodes SGLT2, at the single cell level in multiple datasets, confirming SLC5A2 expression in a subset of kidney epithelial cells but no meaningful expression in other cell types. This was true irrespective of developmental stage, disease state, sequencing method or depth, and species. Our findings support a kidney-centric role for the cardiovascular improvements reported in patients treated with SGLT2i.