title: Teneligliptin improves glycemic control with the reduction of postprandial insulin requirement in Japanese diabetic patients.
abstract: Teneligliptin is a novel peptidomimetic-chemotype prolylthiazolidine-based inhibitor of dipeptidyl peptidase-4 (DPP-4). The aim of this study was to evaluate the effects of teneligliptin on 24 h blood glucose control and gastrointestinal hormone responses to a meal tolerance test, and to investigate the glucose-lowering mechanisms of teneligliptin. Ten patients with type 2 diabetes mellitus (T2DM) were treated for 3 days with teneligliptin (20 mg/day). Postprandial profiles for glucose, insulin, glucagon, active glucagon-like peptide-1 (GLP-1), active glucose-dependent insulinotropic polypeptide (GIP), ghrelin, des-acyl ghrelin, and 24 h glycemic fluctuations were measured via continuous glucose monitoring for 4 days. Once daily teneligliptin administration for 3 days significantly lowered postprandial and fasting glucose levels. Significant elevations of fasting and postprandial active GLP-1 and postprandial active GIP levels were observed. Teneligliptin lowered postprandial glucose elevations, 24 h mean blood glucose levels, standard deviation of 24 h glucose levels and mean amplitude of glycemic excursions (MAGE) without hypoglycemia. Serum insulin levels in the fasting state and 30 min after a meal were similar before and after teneligliptin treatment; however significant reductions at 60 to 180 min after treatment were observed. A significant elevation in early-phase insulin secretion estimated by insulinogenic and oral disposition indices, and a significant reduction in postprandial glucagon AUC were observed. Both plasma ghrelin and des-acyl ghrelin levels were unaltered following teneligliptin treatment. Teneligliptin improved 24 h blood glucose levels by increasing active incretin levels and early-phase insulin secretion, reducing the postprandial insulin requirement, and reducing glucagon secretion. Even short-term teneligliptin treatment may offer benefits for patients with T2DM.
authors.affiliation: Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan.
authors.forename: Wakaba
authors.initials: W
authors.lastname: Tsuchimochi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ueno
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Yamashita
authors.forename: Chikako
authors.initials: C
authors.lastname: Tsubouchi
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sakoda
authors.forename: Shuji
authors.initials: S
authors.lastname: Nakamura
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Nakazato
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D003131:Combined Modality Therapy / Q000009:adverse effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000628:therapy; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000819:agonists / Q000097:blood; D005934:Glucagon / Q000037:antagonists & inhibitors / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000819:agonists / Q000097:blood; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control*; D007003:Hypoglycemia / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D007333:Insulin Resistance; D007564:Japan; D008875:Middle Aged; D018670:Monitoring, Ambulatory; D019518:Postprandial Period; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D053778:Thiazolidines / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: C579035:3-(4-(4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl)pyrrolidin-2-ylcarbonyl)thiazolidine; D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D011720:Pyrazoles; D053778:Thiazolidines; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon