title: Pharmacokinetic and pharmacodynamic interaction between gemigliptin and metformin in healthy subjects.
abstract: OBJECTIVE
  Gemigliptin is a novel dipeptidyl peptidase-4 (DPP-4) inhibitor used in the treatment of type 2 diabetes mellitus. This study evaluated possible pharmacodynamic and pharmacokinetic interactions between gemigliptin and metformin and investigated their tolerability.
  
  
  METHODS
  A randomized, open-label, multiple-dose, three-treatment, three-period, three-sequence crossover study was conducted in healthy male subjects. Twenty-seven subjects received gemigliptin (50 mg once daily), metformin (1,000 mg twice a day), or both drugs for 7 days per dosing period. Blood samples were drawn over 24 h on the seventh day of each period for pharmacokinetic and pharmacodynamic evaluations, including plasma DPP-4 activity and total/active glucagon-like peptide-1 (GLP-1) levels. Meal tolerance tests were conducted for pharmacodynamic assessment on the eighth day. Safety and tolerability were evaluated using adverse events, vital signs, ECGs, and clinical laboratory tests.
  
  
  RESULTS
  Coadministration of gemigliptin and metformin had no significant effect on the pharmacokinetics of gemigliptin or metformin. The inhibition of DPP-4 by gemigliptin was not affected by coadministration with metformin. Co-therapy of gemigliptin and metformin showed additional effects by increasing plasma active GLP-1 concentrations and lowering serum glucose levels. The plasma glucagon level was lower in co-therapy than with metformin monotherapy. The coadministration of gemigliptin and metformin was well-tolerated without serious adverse events.
  
  
  CONCLUSIONS
  Coadministration of gemigliptin and metformin showed beneficial anti-diabetic effects without pharmacokinetic drug-drug interactions.
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea.
authors.forename: Dongseong
authors.initials: D
authors.lastname: Shin
authors.forename: Young Min
authors.initials: YM
authors.lastname: Cho
authors.forename: SeungHwan
authors.initials: S
authors.lastname: Lee
authors.forename: Kyoung Soo
authors.initials: KS
authors.lastname: Lim
authors.forename: Jeong-Ae
authors.initials: JA
authors.lastname: Kim
authors.forename: Ji-Yung
authors.initials: JY
authors.lastname: Ahn
authors.forename: Joo-Youn
authors.initials: JY
authors.lastname: Cho
authors.forename: Howard
authors.initials: H
authors.lastname: Lee
authors.forename: In-Jin
authors.initials: IJ
authors.lastname: Jang
authors.forename: Kyung-Sang
authors.initials: KS
authors.lastname: Yu
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000187:drug effects; D018592:Cross-Over Studies; D018819:Dipeptidyl Peptidase 4 / Q000187:drug effects / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D004347:Drug Interactions; D005934:Glucagon / Q000097:blood / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D008875:Middle Aged; D010881:Piperidones / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D011743:Pyrimidines / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; C534891:LC15-0444; D010881:Piperidones; D011743:Pyrimidines; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D008687:Metformin; D018819:Dipeptidyl Peptidase 4