ARRY-403 is a novel glucokinase activator that reduces fasting and postprandial blood glucose in patients with type 2 diabetes.

Phase I studies have shown that ARRY-403 (AMG 151) activates glucokinase, a key enzyme in glucose homeostasis. The present randomized, placebo-controlled phase IIa study evaluated the dose-effect relationship of the glucokinase activator AMG 151 relative to placebo on fasting plasma glucose (FPG) in 236 patients (33-35 patients per arm) with type 2 diabetes treated with metformin. Patients received oral AMG 151 at 50, 100, or 200 mg twice daily, AMG 151 at 100, 200, or 400 mg once daily, or matching placebo for 28 days. A significant linear dose-effect trend was observed with the twice-daily regimen (p = 0.004) for change in FPG to day 28. No trend was observed with the once-daily regimen. A higher incidence of hypoglycemia and hypertriglyceridemia was observed with AMG 151 administration. AMG 151 significantly reduced FPG when administered twice daily but not when administered once daily in patients with type 2 diabetes treated with metformin.[1]