Comparison of the Effects of Mitiglinide and Glibenclamide Administered in Combination with the Dipeptidyl Peptidase-IV Inhibitor Sitagliptin in Rats with Streptozotocin-Nicotinamide-Induced Type 2 Diabetes

Drug Res (Stuttg). 2017 Jul;67(7):396-403. doi: 10.1055/s-0043-102951. Epub 2017 May 9.

Abstract

We compared the individual effects of mitiglinide and glibenclamide administered in combination with the dipeptidyl peptidase-IV (DPP-IV) inhibitor sitagliptin on plasma DPP-IV activity and blood glucose levels in rats with streptozotocin-nicotinamide-induced type 2 diabetes (STZ-NA rats). We examined the inhibitory activity of mitiglinide and glibenclamide as well as their combination with sitagliptin on plasma DPP-IV activity in STZ-NA rats. The oral glucose tolerance test (OGTT) was used to compare effects of mitiglinide, glibenclamide, and their combination with sitagliptin on blood glucose levels in STZ-NA rats. Mitiglinide and glibenclamide did not inhibit rat DPP-IV and did not influence the inhibitory effect of sitagliptin on rat plasma DPP-IV activity. In STZ-NA rats, plasma glucose levels were stronger suppressed by a combination of mitiglinide and sitagliptin than by either drug used alone. However, no clear effect of the combination of glibenclamide and sitagliptin was observed. These results indicate that the combination of mitiglinide and sitagliptin has a lower risk of hypoglycemia in the rats with induced type 2 diabetes compared with the combination of glibenclamide and sitagliptin. The combination of mitiglinide and sitagliptin can be a promising combination for the treatment of diabetic patients.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Blood Glucose / drug effects
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / chemically induced*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / chemically induced*
  • Dipeptidyl-Peptidase IV Inhibitors / administration & dosage
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology*
  • Drug Synergism
  • Glucose Tolerance Test
  • Glyburide / administration & dosage
  • Glyburide / pharmacology*
  • Isoindoles / administration & dosage
  • Isoindoles / pharmacology*
  • Male
  • Rats
  • Sitagliptin Phosphate / administration & dosage
  • Sitagliptin Phosphate / pharmacology*

Substances

  • Blood Glucose
  • Dipeptidyl-Peptidase IV Inhibitors
  • Isoindoles
  • mitiglinide
  • Glyburide
  • Sitagliptin Phosphate