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. 2013 Oct;62(10):3324-8.
doi: 10.2337/db13-0604.

Novel hypothesis to explain why SGLT2 inhibitors inhibit only 30-50% of filtered glucose load in humans

Muhammad A Abdul-Ghani  1 , Ralph A DeFronzo, Luke Norton
Affiliations

Novel hypothesis to explain why SGLT2 inhibitors inhibit only 30-50% of filtered glucose load in humans

Muhammad A Abdul-Ghani et al. Diabetes. 2013 Oct.

Abstract

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.

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Figures

FIG. 1.
FIG. 1.
Renal glucose reabsorption in the proximal tubule in NGT individuals under physiologic conditions.
FIG. 2.
FIG. 2.
Relationship between glucose filtration load (GFL) and UGE and the plasma glucose concentration under physiologic conditions and during maximal inhibition of SGLT2.
FIG. 3.
FIG. 3.
Renal glucose reabsorption in the proximal tubule in NGT individuals under complete SGLT2 inhibition.
FIG. 4.
FIG. 4.
Predicted relationship between the fraction of filtered glucose excreted in the urine and the plasma glucose concentration during maximal inhibition of SGLT2. The maximal SGLT1 transport capacity was estimated at 120 g/day (see text for details). GFL, glucose filtration load.
FIG. 5.
FIG. 5.
Predicted fold increase in the level of glucosuria produced by SGLT2 inhibitors in relation to the percent inhibition of SGLT1 activity.
See this image and copyright information in PMC

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