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

Cell Metab. 2017 Jul 5;26(1):27-38. doi: 10.1016/j.cmet.2017.04.011. Epub 2017 May 11.


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.

Keywords: SGLT2 inhibition; diabetes; ketogenesis; lipid oxidation; sodium-glucose co-transporters.

Publication types

  • Review

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Brain / drug effects
  • Brain / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism
  • Drug Discovery* / methods
  • Energy Metabolism / drug effects
  • Glucose / metabolism
  • Heart / drug effects
  • Hemodynamics / drug effects
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Kidney / drug effects
  • Kidney / metabolism
  • Metabolic Networks and Pathways / drug effects
  • Protective Agents / pharmacology*
  • Sodium-Glucose Transporter 2 / metabolism*
  • Sodium-Glucose Transporter 2 Inhibitors*


  • Blood Glucose
  • Hypoglycemic Agents
  • Protective Agents
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors
  • Glucose