title: AMG 151 (ARRY-403), a novel glucokinase activator, decreases fasting and postprandial glycaemia in patients with type 2 diabetes.
abstract: Phase I studies have shown that 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 hypoglycaemia and hypertriglyceridaemia 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.
authors.affiliation: Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Katz
authors.affiliation: Amgen Ltd, Cambridge, UK.
authors.forename: N
authors.initials: N
authors.lastname: Manamley
authors.affiliation: Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: W J
authors.initials: WJ
authors.lastname: Snyder
authors.affiliation: Amgen Inc., Seattle, WA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Dodds
authors.affiliation: Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Agafonova
authors.affiliation: Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Sierra-Johnson
authors.affiliation: Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Cruz
authors.affiliation: Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Kaur
authors.affiliation: Center for Metabolic Research, Veterans Administration San Diego Healthcare System, San Diego, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Mudaliar
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: P
authors.initials: P
authors.lastname: Raskin
authors.affiliation: Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Kewalramani
authors.affiliation: Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Pellacani
mesh_terms: D000328:Adult; D000631:Aminopyridines / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D015507:Drugs, Investigational / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D020536:Enzyme Activators / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D005500:Follow-Up Studies; D005941:Glucokinase / Q000737:chemistry / Q000378:metabolism*; D006442:Glycated Hemoglobin / Q000032:analysis; D006261:Headache / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D006943:Hyperglycemia / Q000453:epidemiology / Q000517:prevention & control*; D015228:Hypertriglyceridemia / Q000139:chemically induced / Q000453:epidemiology; D007003:Hypoglycemia / Q000139:chemically induced / Q000453:epidemiology / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D015994:Incidence; D016018:Least-Squares Analysis; D019518:Postprandial Period; D013830:Thiadiazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood
chemical_list: D000631:Aminopyridines; D001786:Blood Glucose; D015507:Drugs, Investigational; D020536:Enzyme Activators; D005941:Glucokinase; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D013830:Thiadiazoles; D014280:Triglycerides; C000611842:ARRY-403; C517652:hemoglobin A1c protein, human
keywords: antidiabetic drug; clinical trial; dose-response relationship; glucokinase activator; type 2 diabetes