Lexicon Pharmaceuticals announced updated data from a Phase 2b clinical trial of LX4211 for type 2 diabetes mellitus. LX4211, an investigational, oral, dual inhibitor of sodium glucose co-transporters 1 and 2 (SGLT1 and SGLT2), reduces the amount of glucose that enters the bloodstream from the gastrointestinal (GI) tract by inhibiting SGLT1, the major transporter responsible for glucose absorption, and enhances glucose excretion in the urine by inhibiting SGLT2, the major transporter responsible for glucose reabsorption by the kidney.
In the trial, LX4211 was tested in 299 patients with poorly controlled type 2 diabetes on metformin therapy. Patients were randomized to receive LX4211 at doses of 75mg daily, 200mg daily, 200mg twice daily, 400mg daily, or placebo for 12 weeks. New data showed that maximal 24-hour urinary glucose excretion occurred at the 200mg daily dose, whereas maximal HbA1c reduction was obtained at the 400mg daily dose. This suggests that dual inhibition of SGLT1 and SGLT2 offers the opportunity to achieve improved glycemic control with lower urinary glucose excretion relative to compounds that are selective for SGLT2. These findings are consistent with previous studies that indicate LX4211’s inhibition of SGLT1 in the GI tract reduces post-prandial glucose levels, resulting in a lower glucose load to be filtered by the kidney.
Consistent with previous reports, the primary efficacy endpoint of change from baseline to Week 12 in HbA1c was achieved; dose dependent changes from placebo were observed with statistically significant differences observed at each dose level and most notably at the higher doses with P<0.001. Lexicon has also previously demonstrated that SGLT1 inhibition by LX4211 increases levels of GLP-1 and PYY, GI hormones associated with glycemic control and appetite.
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