Lexicon Pharmaceuticals,
Inc. LXRX, a biopharmaceutical company focused on discovering
breakthrough treatments for human disease, presented the first publication of
data on LX2761 at the 73^rd Scientific Sessions of the American Diabetes
Association (ADA) in Chicago, on June 23, 2013.
David Powell, M.D., Lexicon's senior vice president of metabolism research,
delivered an oral presentation titled "LX2761, an SGLT1 Inhibitor Restricted
to the Intestine, Improves Glycemic Control in Mice." Dr. Powell's
presentation described the effects of LX2761 treatment on blood sugar control
in mice with diabetes.
"LX2761 was designed to act locally in the gastrointestinal tract to reduce
glucose absorption by inhibiting SGLT1 without any significant inhibition of
SGLT2 in the kidney," said Alan Main, Ph.D., Lexicon's executive vice
president of pharmaceutical research. "This was accomplished through a
dedicated medicinal chemistry effort to identify molecules with limited
systemic exposure that showed efficacy in animal models of diabetes."
Consistent with design goals for an SGLT1 inhibitor without systemic exposure,
LX2761 resulted in no urinary glucose excretion in mice while showing delayed
intestinal glucose absorption and increased postprandial GLP-1 levels in mice,
both alone and synergistically with the DPP-4 inhibitor sitagliptin. Notably,
blood glucose excursions after an oral glucose challenge were still decreased
15 hours after oral LX2761 administration. Finally, LX2761 improved glycemic
control in STZ-diabetic mice and in the KKAy mouse model of type 2 diabetes,
as measured by reductions in hemoglobin A1c and oral glucose tolerance test
results.
"We hope LX2761 may one day treat a large population of patients with
diabetes, and potentially prediabetes, that may wish to avoid the urinary
glucose excretion associated with SGLT2 inhibition in the kidney," said Brian
Zambrowicz, Ph.D., executive vice president and chief scientific officer. "In
addition, the synergy demonstrated with a DPP-4 inhibitor provides the
mechanistic rationale to consider future combination therapies."
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