PHILADELPHIA – An investigational glucokinase activator lowered glucose levels without producing hypoglycemia in a 2-week, phase IIa study of 60 patients with type 2 diabetes.
The enzyme glucokinase (GK) is involved in glucose homeostasis via control of both pancreatic insulin secretion and glucose disposal in the liver. The compound GKM-001, under development by Advinus Therapeutics, differs from other investigational GK activators in that it specifically targets the liver and avoids the pancreas, thereby eliminating the risk for hypoglycemia, Rashmi H. Barbhaiya, Ph.D., said at the annual scientific sessions of the American Diabetes Association.
In a multiple ascending dose study, 60 patients were washed out of their prior medications, then randomized either to doses of 25, 50, 200, 600, or 1,000 mg or to placebo.
Compared with baseline, there were dose-dependent reductions in the 24-hour glucose area under the curve. At day 14, the percent reductions were 9% with 25 mg, 14% with 50 mg, 15% with 200 mg, 17% with 600 mg, and 20% with 1,000 mg, while the placebo group had a 2% increase. Significant reductions were also seen in fasting glucose levels, ranging from 23 to 46 mg/dL, reported Dr. Barbhaiya, CEO and managing director of Advinus, which is based in Bangalore, India.
No hypoglycemia was seen with any of the doses following 12 hours of overnight fasting and 2 hours of postdose fasting, he said.
Neither oral glucose tolerance tests nor dinnertime mixed-meal tolerance tests on days 1 and 14 showed any changes in C-peptide area under the curve, providing further evidence that GKM-001 is not interacting with the pancreas and that its glucose-lowering action is not due to increased insulin levels, he said.
There were also no changes in levels of plasma triglycerides, aspartate transaminase, or alanine aminotransferase.
The company will soon be initiating a phase IIb study of GKM-001 that will assess its impact on hemoglobin A1c levels when used in combination with metformin, he said.
The study was funded by Advinus Therapeutics. Dr. Barbhaiya is a cofounder and a shareholder of the company.