Novel Hypothesis to Explain Why SGLT2 Inhibitors Inhibit Only 30–50% of Filtered Glucose Load in Humans

  1. Luke Norton
  1. Division of Diabetes, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
  1. Corresponding author: Muhammad A. Abdul-Ghani, abdulghani{at}


Inhibitors of sodium-glucose cotransporter 2 (SGLT2) are a novel class of antidiabetes drugs, and members of this class are under various stages of clinical development for the management of type 2 diabetes mellitus (T2DM). It is widely accepted that SGLT2 is responsible for >80% of the reabsorption of the renal filtered glucose load. However, maximal doses of SGLT2 inhibitors fail to inhibit >50% of the filtered glucose load. Because the clinical efficacy of this group of drugs is entirely dependent on the amount of glucosuria produced, it is important to understand why SGLT2 inhibitors inhibit <50% of the filtered glucose load. In this Perspective, we provide a novel hypothesis that explains this apparent puzzle and discuss some of the clinical implications inherent in this hypothesis.

  • Received April 16, 2013.
  • Accepted July 9, 2013.

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 for details.

| Table of Contents