Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) announced today the publication of results from two initial trials of LX4211 in patients with type 2 diabetes in the online edition of the journal Clinical Pharmacology & Therapeutics. The paper, containing results from both trials, is entitled, "LX4211, a Dual SGLT1/SGLT2 Inhibitor, Improved Glycemic Control in Patients with Type 2 Diabetes in a Randomized, Placebo-controlled Trial," and will also appear in an upcoming print edition of the journal. A link to the online article can be accessed at http://www.nature.com/clpt/journal/vaop/ncurrent/full/clpt201258a.html.
"This publication represents the first peer-reviewed description of SGLT1 inhibition stimulating GLP-1 and PYY release in man," said Dr. Brian Zambrowicz, Lexicon's executive vice president and chief scientific officer. "Since LX4211 also inhibits SGLT2, the rapid and significant glycemic control and metabolic benefits observed may be attributed to effective dual inhibition of these two targets."
In the 4-week Phase 2a study described in the paper, 36 patients received once-daily oral administration of placebo or 150 mg or 300 mg of LX4211 (randomized 1:1:1) in an in-patient setting. Patients receiving LX4211 exhibited rapid and significant improvements relative to placebo in multiple measures of glycemic control, including hemoglobin A1c (HbA1c), fasting plasma glucose, and oral glucose tolerance. In addition, serum triglycerides were significantly lower at the end of the four-week treatment period, and trends of meaningful reductions in body weight and blood pressure were observed. Importantly, LX4211 treatment demonstrated a favorable safety profile and was well tolerated in the study. Also described in the paper was a subsequent clinical study conducted in a similar population of poorly-controlled patients with type 2 diabetes that showed LX4211 treatment elevated GLP-1 and PYY, two gastrointestinal peptides known to be associated with enhanced metabolic control. These elevations in GLP-1 levels after LX4211 treatment were previously suggested by data from the Phase 2a study and, hence, the repeated observation confirmed that LX4211 can act as an oral, GLP-1 secretagogue.
Lexicon recently reported top-line results from a Phase 2b double-blind study of LX4211 that extend favorable observations of the early trials to an out-patient setting in a larger population with a longer duration of therapy. The 12-week study was conducted at more than 50 centers in the United States in 299 patients with poorly-controlled diabetes despite treatment with metformin, an established diabetes therapy. Primary and secondary measures of efficacy from this study demonstrated substantial, dose-dependent, statistically-significant reductions in HbA1c, body weight and blood pressure. LX4211's dual inhibition of SGLT1 and 2 was associated with an overall favorable safety profile in the study and, notably, LX4211's inhibition of SGLT1 was associated with a favorable gastrointestinal safety profile similar to placebo.
Lexicon Pharmaceuticals, Inc.