Lexicon Pharmaceuticals reported positive data from a recently completed clinical trial and mechanistic study of LX4211, a dual inhibitor of the sodium glucose transporters 1 and 2 (SGLT1 and SGLT2). The favorable safety profile and effects on multiple parameters of glycemic control and cardiovascular health in healthy normal subjects support the broad potential of LX4211 in the treatment of diabetes and associated metabolic conditions.
Results from the study demonstrated that the 400 mg solid oral dose of LX4211 compared to placebo significantly reduced mean changes from baseline in fasting plasma glucose and post-prandial glucose levels in parallel with meaningful mean increases from baseline in total and active GLP-1 as well as PYY. GLP-1 is associated with improved glucose control and decreased food intake through reduction of appetite. PYY is a gastrointestinal-derived peptide hormone that has also been associated with reducing food intake and has been studied as an anti-obesity agent.
These two gastrointestinal peptides are secreted into circulation by neuroendocrine cells as part of a natural homeostatic mechanism that senses nutrient transit through the gastrointestinal tract. Such nutrient sensing and related mechanisms are thought to be enhanced as a result of certain types of bariatric surgery for weight loss and control of diabetes.
LX4211 treatment also produced a 50.2 mg/dL adjusted mean decrease from baseline in triglycerides, consistent with the triglyceride reduction observed in the phase IIa study in type 2 diabetics. In addition, LX4211, compared to placebo, produced a significant adjusted mean decrease in serum uric acid.
Serum uric acid is an emerging marker for cardiovascular risk and renal disease. These data, together with a trend of improved blood pressure observed in the phase IIa study, demonstrate that LX4211 has effects on multiple cardiovascular and metabolic risk factors. Also of importance in this study was the safety of LX4211, which showed no hypoglycemia and no abdominal pain or diarrhea, consistent with the favorable safety profile associated with dual inhibition of SGLT1 and SGLT2 by LX4211 in previous clinical trials.