AMG 151 (ARRY-403), a novel glucokinase activator, decreases fasting and postprandial glycaemia in patients with type 2 diabetes

L. Katz, N. Manamley, W. J. Snyder, M. Dodds, N. Agafonova, J. Sierra-Johnson, M. Cruz, P. Kaur, S. Mudaliar, Philip Raskin, R. Kewalramani, A. Pellacani

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 200mg twice daily, AMG 151 at 100, 200 or 400mg once daily or matching placebo for 28days. A significant linear dose-effect trend was observed with the twice-daily regimen (p=0.004) for change in FPG to day28. 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.

Original languageEnglish (US)
Pages (from-to)191-195
Number of pages5
JournalDiabetes, Obesity and Metabolism
Volume18
Issue number2
DOIs
StatePublished - Feb 1 2016

Fingerprint

Glucokinase
Type 2 Diabetes Mellitus
Fasting
Glucose
Metformin
Placebos
Hypertriglyceridemia
Hypoglycemia
Homeostasis
Incidence
Enzymes

Keywords

  • Antidiabetic drug
  • Clinical trial
  • Dose-response relationship
  • Glucokinase activator
  • Type 2 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Katz, L., Manamley, N., Snyder, W. J., Dodds, M., Agafonova, N., Sierra-Johnson, J., ... Pellacani, A. (2016). AMG 151 (ARRY-403), a novel glucokinase activator, decreases fasting and postprandial glycaemia in patients with type 2 diabetes. Diabetes, Obesity and Metabolism, 18(2), 191-195. https://doi.org/10.1111/dom.12586

AMG 151 (ARRY-403), a novel glucokinase activator, decreases fasting and postprandial glycaemia in patients with type 2 diabetes. / Katz, L.; Manamley, N.; Snyder, W. J.; Dodds, M.; Agafonova, N.; Sierra-Johnson, J.; Cruz, M.; Kaur, P.; Mudaliar, S.; Raskin, Philip; Kewalramani, R.; Pellacani, A.

In: Diabetes, Obesity and Metabolism, Vol. 18, No. 2, 01.02.2016, p. 191-195.

Research output: Contribution to journalArticle

Katz, L, Manamley, N, Snyder, WJ, Dodds, M, Agafonova, N, Sierra-Johnson, J, Cruz, M, Kaur, P, Mudaliar, S, Raskin, P, Kewalramani, R & Pellacani, A 2016, 'AMG 151 (ARRY-403), a novel glucokinase activator, decreases fasting and postprandial glycaemia in patients with type 2 diabetes', Diabetes, Obesity and Metabolism, vol. 18, no. 2, pp. 191-195. https://doi.org/10.1111/dom.12586
Katz, L. ; Manamley, N. ; Snyder, W. J. ; Dodds, M. ; Agafonova, N. ; Sierra-Johnson, J. ; Cruz, M. ; Kaur, P. ; Mudaliar, S. ; Raskin, Philip ; Kewalramani, R. ; Pellacani, A. / AMG 151 (ARRY-403), a novel glucokinase activator, decreases fasting and postprandial glycaemia in patients with type 2 diabetes. In: Diabetes, Obesity and Metabolism. 2016 ; Vol. 18, No. 2. pp. 191-195.
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