Novel hypothesis to explain why SGLT2 inhibitors inhibit only 30-50% of filtered glucose load in humans.
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.
Division of Diabetes, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
Muhammad A
MA
Abdul-Ghani
Ralph A
RA
DeFronzo
Luke
L
Norton
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism*; D004359:Drug Therapy, Combination; D006442:Glycated Hemoglobin / Q000378:metabolism; D006029:Glycosuria / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000627:therapeutic use; D007668:Kidney / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D051269:Sodium-Glucose Transporter 1 / Q000037:antagonists & inhibitors*; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors
D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D051269:Sodium-Glucose Transporter 1; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C495674:SLC5A1 protein, human; C089180:SLC5A2 protein, human; C495675:Slc5a1 protein, mouse; C490299:Slc5a2 protein, mouse; C517652:hemoglobin A1c protein, human