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
2007 Journal of Pharmacological Sciences  
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
more » ... 4 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.
doi:10.1254/jphs.fp0061376 pmid:17485917 fatcat:kn25suc6szdhphiolezwq4saca