Metabolic and Hemodynamic Effects of Sodium-Dependent Glucose Cotransporter 2 Inhibitors on Cardio-Renal Protection in the Treatment of Patients With Type 2 Diabetes Mellitus

J Diabetes Investig. 2017 Jul;8(4):416-427. doi: 10.1111/jdi.12644. Epub 2017 May 12.

Abstract

The specific sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) inhibit glucose reabsorption in proximal renal tubular cells, and both fasting and postprandial glucose significantly decrease because of urinary glucose loss. As a result, pancreatic β-cell function and peripheral insulin action significantly improve with relief from glucose toxicity. Furthermore, whole-body energy metabolism changes to relative glucose deficiency and triggers increased lipolysis in fat cells, and fatty acid oxidation and then ketone body production in the liver during treatment with SGLT2 inhibitors. In addition, SGLT2 inhibitors have profound hemodynamic effects including diuresis, dehydration, weight loss and lowering blood pressure. The most recent findings on SGLT2 inhibitors come from results of the Empagliflozin, Cardiovascular Outcomes and Mortality in Type 2 Diabetes trial. SGLT2 inhibitors exert extremely unique and cardio-renal protection through metabolic and hemodynamic effects, with long-term durability on the reduction of blood glucose, bodyweight and blood pressure. Although a site of action of SGLT2 inhibitors is highly specific to inhibit renal glucose reabsorption, whole-body energy metabolism, and hemodynamic and renal functions are profoundly modulated during the treatment of SGLT2 inhibitors. Previous studies suggest multifactorial clinical benefits and safety concerns of SGLT2 inhibitors. Although ambivalent clinical results of this drug are still under active discussion, the present review summarizes promising recent evidence on the cardio-renal and metabolic benefits of SGLT2 inhibitors in the treatment of type 2 diabetes.

Keywords: Oral hypoglycemic drugs; Sodium-glucose cotransporter 2 inhibitors; Type 2 diabetes mellitus.

Publication types

  • Review

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Cardiovascular Diseases / prevention & control
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Therapy, Combination
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Hypoglycemic Agents / therapeutic use*
  • Ketone Bodies / metabolism
  • Kidney Tubules, Proximal / metabolism
  • Pancreas / metabolism
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors*

Substances

  • Hypoglycemic Agents
  • Ketone Bodies
  • SLC5A2 protein, human
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors