Dear Colleagues,

Sodium-glucose co-transporters (SGLTs) are a family of transmembrane receptors which are variably expressed in the kidney and intestine, and physiologically function in the control of cellular glucose uptake. For example, SGLT1 is responsible for almost all sodium-dependent glucose uptake in the small intestine and approximately 3% in the kidney. In contrast, SGLT2 accounts for more than 90% of glucose reabsorption from the glomerular ultrafiltrate. Since glucose reabsorption is sodium-dependent, SGLTs also play a crucial role in natriuresis, plasma osmolarity, and regulation of plasma volume.

Interest in SGLTs has increased since their inhibition has proven to be an effective glucose-lowering treatment strategy. Moreover, beyond glycemic control, SGLT2 inhibitors have been shown to cause a significant reduction in cardiovascular and renal morbidity, lower hospitalization rates for heart failure, and reduce progression of renal damage and albuminuria in patients with or without diabetes mellitus. SGLT2 inhibitors also seem to reduce blood pressure and benefit weight loss. Their clinical impact has been so important that they have been included not only in diabetes treatment guidelines but also in the treatment of chronic heart failure, and chronic kidney disease and albuminuria regardless of glycemic status. Numerous pharmacological mechanisms for these effects have been hypothesized, although no conclusive evidence is currently available.

The aim of this Special Issue is to provide an update on our current knowledge of the function of SGLTs. The goal of this work is to promote the development of new pharmacodynamic hypotheses, as well as examine the clinical impact of SGLT inhibition on cardiovascular and renal risk independent of the presence of diabetes mellitus.

Dr. Riccardo Nevola

Guest Editor