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Perspectives in Diabetes

Why Do SGLT2 Inhibitors Inhibit Only 30–50% of Renal Glucose Reabsorption in Humans?

  1. Jiwen (Jim) Liu1⇓,
  2. TaeWeon Lee2 and
  3. Ralph A. DeFronzo3⇓
  1. 1Medicinal Chemistry, Amgen, Inc., South San Francisco, California
  2. 2Metabolic Disorders, Amgen, Inc., South San Francisco, California
  3. 3Division of Diabetes, University of Texas Health Science Center at San Antonio, San Antonio, Texas
  1. Corresponding authors: Jiwen (Jim) Liu, jiwenl{at}amgen.com, and Ralph A. DeFronzo, albarado{at}uthscsa.edu.
Diabetes 2012 Sep; 61(9): 2199-2204. https://doi.org/10.2337/db12-0052
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Abstract

Sodium glucose cotransporter 2 (SGLT2) inhibition is a novel and promising treatment for diabetes under late-stage clinical development. It generally is accepted that SGLT2 mediates 90% of renal glucose reabsorption. However, SGLT2 inhibitors in clinical development inhibit only 30–50% of the filtered glucose load. Why are they unable to inhibit 90% of glucose reabsorption in humans? We will try to provide an explanation to this puzzle in this perspective analysis of the unique pharmacokinetic and pharmacodynamic profiles of SGLT2 inhibitors in clinical trials and examine possible mechanisms and molecular properties that may be responsible.

Footnotes

  • This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db12-0052/-/DC1.

  • Received January 17, 2012.
  • Accepted April 10, 2012.
  • © 2012 by the American Diabetes Association.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

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Diabetes: 61 (9)

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September 2012, 61(9)
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Why Do SGLT2 Inhibitors Inhibit Only 30–50% of Renal Glucose Reabsorption in Humans?
Jiwen (Jim) Liu, TaeWeon Lee, Ralph A. DeFronzo
Diabetes Sep 2012, 61 (9) 2199-2204; DOI: 10.2337/db12-0052

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Why Do SGLT2 Inhibitors Inhibit Only 30–50% of Renal Glucose Reabsorption in Humans?
Jiwen (Jim) Liu, TaeWeon Lee, Ralph A. DeFronzo
Diabetes Sep 2012, 61 (9) 2199-2204; DOI: 10.2337/db12-0052
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    • PUZZLE ABOUT SGLT2 INHIBITORS
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  • Closing in on the Mechanisms of Pulsatile Insulin Secretion
  • The Adiponectin Paradox for All-Cause and Cardiovascular Mortality
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