Isis starts study of type II diabetes drug

The glucagon receptor (GCGR) binds glucagon, a hormone that opposes the action of insulin.

The Phase I trial of ISIS 325568 is designed to assess the drug's activity, including its effect on liver glucose production, as well as safety and pharmacokinetic profiles, providing the opportunity to demonstrate proof-of-concept in this first human trial.

The study is a randomized, placebo-controlled, dose-escalation study conducted in healthy volunteers.

“We are excited by the preclinical profile of ISIS 325568, a novel first-in-class drug that has demonstrated excellent glucose control and improved pancreatic function through a dual mechanism of action in insulin-resistant animal models,” said Sanjay Bhanot, vice president of metabolic diseases R&D, Isis Pharmaceuticals.

“Furthermore, the favorable effects on GLP-1 that we have seen exceed those observed with DPP IV inhibitors, and there was no evidence of hypoglycemia or GI side effects. These preclinical findings suggest that ISIS 325568 could offer disease modifying effects and long-term disease control both as a single agent and in combination with other diabetes treatments,” he added.

Glucagon is a hormone that opposes the action of insulin and stimulates the liver to produce glucose. In type II diabetes, unopposed action of glucagon can lead to increased blood glucose levels. Reducing the expression of liver GCGR using antisense inhibitors, and thereby reducing excessive liver glucose production, is expected to lower blood glucose levels and help control type II diabetes, according to the company.

In preclinical studies, antisense inhibitors of GCGR led to improved glucose control and reduced levels of blood triglycerides without producing hypoglycemia. In addition, treatment with ISIS 325568 led to an increase in circulating glucagon-like peptide, or GLP-1, which is a hormone that helps to preserve pancreatic function, thereby enhancing insulin secretion.