title: Lansoprazole enhances the antidiabetic effect of sitagliptin in mice with diet-induced obesity and healthy human subjects.
abstract: OBJECTIVE
  Proton pump inhibitors as adjunctive therapy would improve diabetes control and could enhance the hypoglycaemic activity of DPP-4 inhibitors. The aim of the study was to investigate the short-term effects of lansoprazole (LPZ), sitagliptin (SITA) and their combination therapy on glucose regulation and gut peptide secretion.
  
  
  METHODS
  Glucose and gut peptide were determined and compared after short-term administration of LPZ or SITA, or in combination to mice with diet-induced obesity (DIO) and to healthy human subjects (n = 16) in a 75 g oral glucose tolerance test (OGTT) by a crossover design.
  
  
  RESULTS
  In DIO mice, LPZ significantly improve glucose metabolism, increase plasma C-peptide and insulin compared with vehicle treatment. Furthermore, the combination of LPZ and SITA improved glucose tolerance additively, with higher plasma insulin and C-peptide levels compared with SITA-treated mice. Similarly, in human in the OGTT, the combination showed significant improvement in glucose-lowering and insulin increase vs SITA-treated group. However, no significant differences in area under curve (AUC) of insulin, glucose and C-peptide between the LPZ-treated group and baseline, except that mean AUCgastrin was significantly increased by LPZ.
  
  
  CONCLUSIONS
  LPZ and SITA combination therapy appears to have complementary mechanisms of action and additive antidiabetic effect.
authors.affiliation: Department of Pharmacy and Equipment, No. 371 Hospital of PLA, Xin'xiang, China.
authors.forename: ShaoJun
authors.initials: S
authors.lastname: Hao
authors.forename: JianHua
authors.initials: J
authors.lastname: Sun
authors.forename: XiKui
authors.initials: X
authors.lastname: Tian
authors.forename: Xu
authors.initials: X
authors.lastname: Sun
authors.forename: ZhenXing
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
mesh_terms: D000328:Adult; D000818:Animals; D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects; D002096:C-Peptide / Q000097:blood; D004032:Diet / Q000009:adverse effects; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000379:methods; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test / Q000379:methods; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D064747:Lansoprazole / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000097:blood / Q000188:drug therapy*; D011719:Pyrazines / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D011719:Pyrazines; D014230:Triazoles; D064747:Lansoprazole; D005947:Glucose; D000068900:Sitagliptin Phosphate
keywords: biopharmaceutics and drug disposition; drug disposition in tissues and whole animals; in-vivo/in-vitro correlation; pharmacokinetics and drug disposition