Journal of Pharmacological Sciences (Jan 2007)

Comparison of Efficacies of a Dipeptidyl Peptidase IV Inhibitor and α-Glucosidase Inhibitors in Oral Carbohydrate and Meal Tolerance Tests and the Effects of Their Combination in Mice

  • Kazuto Yamazaki,
  • Takashi Inoue,
  • Nobuyuki Yasuda,
  • Yoshiaki Sato,
  • Tadashi Nagakura,
  • Osamu Takenaka,
  • Richard Clark,
  • Takao Saeki,
  • Isao Tanaka

DOI
https://doi.org/10.1254/jphs.fp0061376
Journal volume & issue
Vol. 104, no. 1
pp. 29 – 38

Abstract

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E3024 (3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate) is a dipeptidyl peptidase IV (DPP-IV) inhibitor. Since the target of both DPP-IV inhibitors and α-glucosidase inhibitors is the lowering of postprandial hyperglycemia, we compared antihyperglycemic effects for E3024 and α-glucosidase inhibitors in various oral carbohydrate and meal tolerance tests using normal mice. In addition, we investigated the combination effects of E3024 and voglibose on blood glucose levels in a meal tolerance test using mice fed a high-fat diet. ER-235516-15 (the trifluoroacetate salt form of E3024, 1 mg/kg) lowered glucose excursions consistently, regardless of the kind of carbohydrate loaded. However, the efficacy of acarbose (10 mg/kg) and of voglibose (0.1 mg/kg) varied with the type of carbohydrate administered. The combination of E3024 (3 mg/kg) and voglibose (0.3 mg/kg) improved glucose tolerance additively, with the highest plasma active glucagon-like peptide-1 levels. This study shows that compared to α-glucosidase inhibitors, DPP-IV inhibitors may have more consistent efficacy to reduce postprandial hyperglycemia, independent of the types of carbohydrate contained in a meal, and that the combination of a DPP-IV inhibitor and an α-glucosidase inhibitor is expected to be a promising option for lowering postprandial hyperglycemia. Keywords:: dipeptidyl peptidase IV inhibitor, α-glucosidase inhibitor, combination effect, tolerance test