title: Additive postprandial glucose-lowering effects of mitiglinide and sitagliptin in patients with type 2 diabetes mellitus.
abstract: BACKGROUND
  The aim of this research was to compare the pharmacodynamics of the combination of mitiglinide and sitagliptin to that of each agent alone in Korean patients with type 2 diabetes mellitus (T2DM).
  
  
  METHODS
  Patients with T2DM received mitiglinide alone, sitagliptin alone, or both drugs together in randomized sequence. A meal tolerance test (MTT) was conducted for each group, and plasma concentrations of glucose, insulin, C-peptide, glucagon, and intact glucagon-like peptide-1, and dipeptidyl peptidase-4 activity were measured from 2 h before breakfast through 4 h after breakfast on day 0 (pretreatment) and day 1 (posttreatment) of each treatment period. Integrated values of these pharmacodynamic variables were analyzed for changes from pretreatment to posttreatment and for differences between the three treatment groups.
  
  
  RESULTS
  Twenty-six patients with glycated hemoglobin A1c level of 7.4% ± 0.6%, fasting plasma glucose concentration of 141 ± 22 mg/dL, postprandial plasma glucose (PPG) concentration of 264 ± 48 mg/dL 1 h after the MTT, and diabetes duration of 3.0 ± 3.1 years (mean ± SD) were included in the study. Compared with mitiglinide or sitagliptin alone, the combination treatment lowered PPG additively (P < 0.001 vs. mitiglinide or sitagliptin alone) and the insulin secretory response (P = 0.03 vs. mitiglinide or sitagliptin alone). The integrated insulin concentrations changed significantly from before to after treatment (P < 0.01), but the change did not differ between the combination and mitiglinide groups. The insulinogenic index increased significantly after the combination treatment (P < 0.001 vs. mitiglinide or sitagliptin alone). The combination of mitiglinide and sitagliptin was generally well tolerated, with no hypoglycemic events.
  
  
  CONCLUSIONS
  The combination of mitiglinide and sitagliptin did not trigger hypoglycemia and controlled postprandial glucose excursion more effectively compared with either drug alone.
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Seoul, Korea.
authors.forename: Jin Ah
authors.initials: JA
authors.lastname: Jung
authors.forename: Kohei
authors.initials: K
authors.lastname: Kaku
authors.forename: Jae Hyeon
authors.initials: JH
authors.lastname: Kim
authors.forename: Jung-Ryul
authors.initials: JR
authors.lastname: Kim
authors.forename: Jae-Wook
authors.initials: JW
authors.lastname: Ko
authors.forename: Soo-Youn
authors.initials: SY
authors.lastname: Lee
authors.forename: Wooseong
authors.initials: W
authors.lastname: Huh
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects; D016001:Confidence Intervals; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis*; D006801:Humans; D007003:Hypoglycemia / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D054833:Isoindoles / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period / Q000187:drug effects*; D011446:Prospective Studies; D011719:Pyrazines / Q000008:administration & dosage*; D012016:Reference Values; D012720:Severity of Illness Index; D000068900:Sitagliptin Phosphate; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage*
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D054833:Isoindoles; D011719:Pyrazines; D000068900:Sitagliptin Phosphate; D014230:Triazoles; C087255:mitiglinide