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LX4211 Enhances Effects of DPP-4 Inhibition in Patients with Type 2 Diabetes

THE WOODLANDS, Texas, Jan. 9, 2012 /PRNewswire/ -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) announced today top-line results from the first clinical study testing the combined effects of LX4211, a novel sodium glucose transporter 1 and 2 (SGLT1 and SGLT2) inhibitor, with the dipeptidyl peptidase 4 (DPP-4) inhibitor, sitagliptin (Januvia®), one of the most widely prescribed diabetes drugs.

"The results of this study are important given that combination therapy is the mainstay of current diabetes treatment," said Dr. Pablo Lapuerta, senior vice president of clinical development and chief medical officer at Lexicon.  "Alone, LX4211 produces rapid improvement in postprandial blood glucose by delaying intestinal glucose absorption and increasing urinary glucose excretion.  When combined, the two agents produce enhanced benefits on blood glucose, insulin, GLP-1 and PYY relative to sitagliptin alone, suggesting these agents work together and could provide additional benefits for patients with type 2 diabetes."

Results from the study in 18 patients with type 2 diabetes showed that single doses of LX4211, a dual inhibitor of SGLT1 and SGLT2, in combination with sitagliptin, produced lower blood glucose levels after meals (postprandial) as compared to treatment with sitagliptin alone (p=0.012).  This enhanced glycemic control was associated with an elevation of active glucagon-like peptide-1 (GLP-1) over treatment with either LX4211 or sitagliptin alone (p<0.001).  Consistent with LX4211 monotherapy effects, LX4211 increased total GLP-1 (p<0.001) and PYY (p=0.014) with reduced insulin levels (p=0.025) when dosed with sitagliptin, all three effects not observed with sitagliptin alone.  Active and total GLP-1 are important mediators of blood sugar and metabolic control and PYY has been shown to suppress appetite.  GLP-1 and PYY are normally released in response to a meal.  All treatment regimens were well tolerated.

"These new clinical results are supported by our recent preclinical studies in mice that show a dramatic increase in active GLP-1 after combination treatment with LX4211 and sitagliptin, an effect that is both synergistic and sustained," said Dr. Brian Zambrowicz, executive vice president and chief scientific officer at Lexicon.  "The combined effects of LX4211 and sitagliptin on active GLP-1 are mediated through SGLT1 inhibition by LX4211.  This ability of LX4211 to synergize with DPP-4 inhibition to further increase active GLP-1 is likely to evolve as a significant differentiating feature from SGLT-2-selective inhibitors which have not been shown to affect GLP-1."

DPP-4 inhibitors, such as sitagliptin, increase active GLP-1 by inhibiting DPP-4, the enzyme responsible for GLP-1 breakdown.  DPP-4 inhibitors have been shown to decrease total GLP-1, a form of the hormone that is thought to have additional beneficial effects on metabolism.  DPP-4 inhibitors are often used in combination with other agents such as metformin.

Top-line results from this study will be presented at the J.P. Morgan Healthcare Conference in San Francisco, California on Wednesday, January 11, 2012 at 9:00 a.m. Pacific Time.  A live webcast of the presentation will be available through Lexicon's corporate website at  An archived version of the presentation will be available for 30 days after the event.

About the Clinical Trial
The mechanistic study was designed to assess pharmacodynamic parameters, including postprandial glucose (PPG), insulin, total and active GLP-1, PYY, and urinary glucose excretion (UGE).  The study was conducted in 18 diabetic patients who received single doses of either LX4211 (400 mg), sitagliptin (100 mg) or LX4211 plus sitagliptin on Days 1, 8, or 15, according to a blinded and balanced 3 x 3 crossover design with a 7-day washout period between each dosing day.  Safety was assessed throughout the study.

About Lexicon
Lexicon is a biopharmaceutical company focused on discovering breakthrough treatments for human disease.  Lexicon currently has four drug programs in mid-stage development for diabetes, irritable bowel syndrome, carcinoid syndrome and rheumatoid arthritis, all of which were discovered by Lexicon's research team.  Lexicon has used its proprietary gene knockout technology to identify more than 100 promising drug targets.  Lexicon has focused drug discovery efforts on these biologically-validated targets to create its extensive pipeline of clinical and preclinical programs.  For additional information about Lexicon and its programs, please visit

Safe Harbor Statement
This press release contains "forward-looking statements," including statements relating to Lexicon's clinical development of LX4211, including characterizations of the results of and projected timing of clinical trials of such compounds, and the potential therapeutic and commercial potential of LX4211.  This press release also contains forward-looking statements relating to Lexicon's growth and future operating results, discovery and development of products, strategic alliances and intellectual property, as well as other matters that are not historical facts or information.  All forward-looking statements are based on management's current assumptions and expectations and involve risks, uncertainties and other important factors, specifically including those relating to Lexicon's ability to successfully conduct clinical development of LX4211 and preclinical and clinical development of its other potential drug candidates, advance additional candidates into preclinical and clinical development, obtain necessary regulatory approvals, achieve its operational objectives, obtain patent protection for its discoveries and establish strategic alliances, as well as additional factors relating to manufacturing, intellectual property rights, and the therapeutic or commercial value of its drug candidates, that may cause Lexicon's actual results to be materially different from any future results expressed or implied by such forward-looking statements.  Unless specifically indicated otherwise, results reported as trends were not statistically significant. Information identifying such important factors is contained under "Risk Factors" in Lexicon's annual report on Form 10-K for the year ended December 31, 2010, as filed with the Securities and Exchange Commission.  Lexicon undertakes no obligation to update or revise any such forward-looking statements, whether as a result of new information, future events or otherwise.


SOURCE Lexicon Pharmaceuticals, Inc.
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