Combination treatment with alogliptin and voglibose increases active GLP-1 circulation, prevents the development of diabetes and preserves pancreatic beta-cells in prediabetic db/db mice

Diabetes Obes Metab. 2010 Mar;12(3):224-33. doi: 10.1111/j.1463-1326.2009.01156.x.


Aim: Alogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, and voglibose, an alpha-glucosidase inhibitor, have different but complementary mechanisms of action on glucagon-like peptide-1 (GLP-1) regulation and glucose-lowering effects. The present study evaluated the chronic effects of combination treatment with alogliptin and voglibose in prediabetic db/db mice.

Methods: Alogliptin (0.03%) and voglibose (0.001%) alone or in combination were administered in the diet to prediabetic db/db mice.

Results: After 3 weeks, voglibose treatment increased GLP-1 secretion (voglibose alone, 1.6-fold; alogliptin plus voglibose, 1.5-fold), while it decreased plasma glucose-dependent insulinotropic polypeptide (GIP) (voglibose alone, -30%; alogliptin plus voglibose, -29%). Alogliptin, voglibose and combination treatment decreased plasma DPP-4 activity by 72, 15 and additively by 80%, respectively, and increased plasma active GLP-1 levels by 4.5-, 1.8- and synergistically by 9.1-fold respectively. Combination treatment increased plasma insulin by 3.6-fold (alogliptin alone, 1.3-fold; voglibose alone, 1.8-fold), decreased plasma glucagon by 30% (alogliptin alone, 11%; voglibose alone, 8%), and prevented the development of diabetes, much more effectively than either agent alone. After 4 weeks, alogliptin, voglibose and combination treatment increased pancreatic insulin content by 1.6-, 3.4- and synergistically by 8.5-fold respectively. Furthermore, combination treatment resulted in an increased expression of insulin, pancreatic and duodenal homeobox 1 (PDX1) and glucose transporter 2 (GLUT2), and maintenance of normal beta/alpha-cell distribution in the pancreatic islet.

Conclusions: Chronic treatment with alogliptin in combination with voglibose concurrently increased active GLP-1 circulation, increased insulin secretion, decreased glucagon secretion, prevented the onset of the disease, and preserved pancreatic beta-cells and islet structure in prediabetic db/db mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / prevention & control*
  • Drug Therapy, Combination / methods
  • Hypoglycemic Agents / administration & dosage*
  • Inositol / administration & dosage
  • Inositol / analogs & derivatives*
  • Insulin-Secreting Cells / drug effects*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Piperidines / administration & dosage*
  • Prediabetic State / drug therapy*
  • RNA-Binding Proteins
  • Transcription Factors / drug effects
  • Uracil / administration & dosage
  • Uracil / analogs & derivatives*


  • Hexim1 protein, mouse
  • Hypoglycemic Agents
  • Piperidines
  • RNA-Binding Proteins
  • Transcription Factors
  • Inositol
  • Uracil
  • alogliptin
  • voglibose