Lexicon’s type 2 diabetes drug has multiple positive effects

Dr. Pablo Lapuerta, senior vice president
of clinical development and chief medical
officer, Lexicon Pharmaceuticals

September 15th, 2011 by Ryan Luce No Comments

written by Michael O’Leary

Could one drug prevent type 2 diabetes in people at risk for the disease, lower blood glucose levels in those already diagnosed, while reducing triglycerides and suppressing appetite?

Lexicon Pharmaceuticals, a Woodland, Texas drug maker says its new drug, LX4211 can do all of that based on early clinical trial results. The drug limits the action of sodium glucose transporters 1 and 2 (SGLT1 and SGLT2), which work to move glucose through certain cell membranes in the intestines. (Link to published site)

The company will present the results of the just completed study this week at the European Association for the Study of Diabetes (EASD) annual meeting in Lisbon, Portugal.

The study, called a pharmacodynamics study, was designed to test the effects of the drug on the body and learn about the drug’s mechanisms of action in healthy people without diabetes. This type of study is usually done with compounds that mimic naturally occurring compounds in the body to see that the drugs do act the same way the natural compounds do. In this case the researchers wanted to see if LX4211 increases levels of two proteins in the body that regulate blood glucose levels and appetite.

In the study, participants were randomly assigned to a group that took a 400 mg dose LX4211 in an ordered sequence to assess the drug’s effects at different dosing times, ranging from 1 hour prior to meals to immediately prior to meals. The effects they measured included glucose in the urine, fasting blood sugar, insulin, PYY and GLP-1 (total and active). These were assessed at multiple time points during the 12-day dosing period. The other group received a non-active placebo.

GLP-1 is short for glucon-like peptide-1 and plays a role in controlling glucose in the blood and curbing the appetite. PYY stands for peptide tyrosine tyrosine. It is a gut hormone that also reduces appetite among other roles in digestion and has been studied as an anti-obesity agent. Both of these chemicals are naturally released into the blood stream by intestinal cells in response to major nutrients such as carbohydrates, proteins and fats in the small intestine.

The results announced by the company showed that of LX4211 significantly increased the levels of GLP-1 and PYY, and reduced post-meal spikes in glucose levels. The drug also produced a 50 milligram per deciliter decrease in triglyceride levels and lowered the levels of uric acid in the blood, which may be a marker for cardiovascular risk and kidney disease.

“We have now observed results from several clinical studies of LX4211,” said Dr. Pablo Lapuerta, senior vice president of clinical development and chief medical officer, “which consistently support the concept of dual SGLT1/SGLT2 inhibition for the treatment of diabetes and indicate a long-term opportunity in diabetes prevention.

Lexicon has completed several clinical trials of the drug in people with type 2 diabetes. This is the first to be tested in healthy people. The company is currently recruiting for another trial (NCT01376557) using the drug with metformin in type 2 diabetes patients with inadequate blood sugar control on metformin alone.