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

Lexicon Pharmaceuticals, Inc. 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.