title: Very short-term effects of the dipeptidyl peptidase-4 inhibitor sitagliptin on the secretion of insulin, glucagon, and incretin hormones in Japanese patients with type 2 diabetes mellitus: analysis of meal tolerance test data.
abstract: BACKGROUND
  Sitagliptin inhibits dipeptidyl peptidase-4, which inactivates the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide. To assess its antidiabetic potency, we used meal tolerance tests (MTTs) to determine the very short-term effects of sitagliptin on plasma concentrations of insulin and glucagon.
  
  
  METHODS
  On day 1, patients with newly diagnosed or uncontrolled type 2 diabetes mellitus started a calorie-restricted diet. On day 2, the first MTT was performed, before treatment with sitagliptin 50 mg/day started later the same day. On day 5, a second MTT was performed. Area under the concentration-time curves (AUCs) of relevant laboratory values were calculated [AUC from time zero to 2 h (AUC0-2h) and from time zero to 4 h (AUC0-4h)].
  
  
  RESULTS
  Fifteen patients were enrolled. AUCs for postprandial plasma glucose were decreased after 3 days of sitagliptin treatment [AUC0-2h 457 ± 115 mg/dL·h (25.4 ± 6.4 mmol/L·h) to 369 ± 108 mg/dL·h (20.5 ± 6.0 mmol/L·h); AUC0-4h 896 ± 248 mg/dL·h (49.7 ± 13.8 mmol/L·h) to 701 ± 246 mg/dL·h (38.9 ± 13.7 mmol/L·h); both p < 0.001]. AUC0-2h and AUC0-4h for postprandial plasma glucagon also decreased: 195 ± 57 to 180 ± 57 pg/mL·h (p < 0.05) and 376 ± 105 to 349 ± 105 pg/mL·h (p < 0.01), respectively. The AUC0-2h [median with quartile values (25%, 75%)] for active GLP-1 increased: 10.5 (8.5, 15.2) to 26.4 (16.7, 32.4) pmol/L·h (p = 0.03).
  
  
  CONCLUSIONS
  Very short-term (3-day) treatment with sitagliptin decreases postprandial plasma glucose significantly. This early reduction in glucose may result partly from suppression of excessive glucagon secretion, through a direct effect on active GLP-1. Improvement in postprandial plasma glucose, through suppression of glucagon secretion, is believed to be an advantage of sitagliptin for the treatment of patients with type 2 diabetes.
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Murai
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Katsuno
authors.forename: Jun-ichiro
authors.initials: J
authors.lastname: Miyagawa
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Matsuo
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Ochi
authors.forename: Masaru
authors.initials: M
authors.lastname: Tokuda
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kusunoki
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miuchi
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Namba
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D005260:Female; D005502:Food; D005934:Glucagon / Q000097:blood / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000378:metabolism; D006801:Humans; D054795:Incretins / Q000097:blood / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D000068900:Sitagliptin Phosphate / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D054795:Incretins; D007328:Insulin; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D000068900:Sitagliptin Phosphate