LX4211 [(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol] decreases renal glucose reabsorption by inhibiting sodium/glucose cotransporter (SGLT)2 and intestinal glucose absorption by inhibiting SGLT1. Clinically, LX4211 improves glycemic control while increasing levels of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) in patients with diabetes. In mice treated with LX4211 and in SGLT1−/− mice, similar increases in GLP-1 and PYY were observed along with increased intestinal glucose and decreased blood glucose excursions after a glucose-containing meal. In contrast, SGLT2−/− mice showed no response, suggesting that LX4211 reduces intestinal glucose absorption by inhibiting SGLT1, resulting in net increases in GLP-1 and PYY release and decreases in blood glucose excursions.
See article at J Pharmacol Exp Ther 2013, 345:250–259.
- Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics