Sodium-Glucose Co-transporters and Their Inhibition: Clinical Physiology

Cell Metabolism
Ele Ferrannini

Abstract

Sodium-glucose cotransporter-2 (SGLT2) is selectively expressed in the human kidney, where it executes reabsorption of filtered glucose with a high capacity; it may be overactive in patients with diabetes, especially in the early, hyperfiltering stage of the disease. As a therapeutic target, SGLT2 has been successfully engaged by orally active, selective agents. Initially developed as antihyperglycemic drugs, SGLT2 inhibitors have deployed a range of in vivo actions. Consequences of their primary effect, i.e., profuse glycosuria and natriuresis, involve hemodynamic (plasma volume and blood pressure reduction) and metabolic pathways (increase in lipid oxidation and ketogenesis at the expense of carbohydrate utilization); the hormonal mediation extends to insulin, glucagon, and gastrointestinal peptides. Their initial trial in high-risk patients with diabetes has provided evidence for marked reduction of cardiovascular risk. This review focuses on the quantitative pharmacology of SGLT2 inhibitors, which can be exploited to discover new physiology, in the heart, kidney, and brain.

References


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Citations

Feb 20, 2018·The Journal of Clinical Hypertension·Kazuomi KarioEle Ferrannini
Dec 8, 2017·British Medical Bulletin·Sagen Zac-Varghese, Peter Winocour
Dec 19, 2017·European Journal of Heart Failure·Angelo Avogaro
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