title: A novel, potent, and long-lasting dipeptidyl peptidase-4 inhibitor, teneligliptin, improves postprandial hyperglycemia and dyslipidemia after single and repeated administrations.
abstract: Dipeptidyl peptidase-4 (DPP-4) inhibitors have been demonstrated to improve glycemic control, in particular postprandial hyperglycemic control, in patients with type 2 diabetes. Teneligliptin is a novel chemotype prolylthiazolidine-based DPP-4 inhibitor. The present study aimed to characterize the pharmacological profiles of teneligliptin in vitro and in vivo. Teneligliptin competitively inhibited human plasma, rat plasma, and human recombinant DPP-4 in vitro, with IC(50) values of approximately 1 nmol/l. Oral administration of teneligliptin in Wistar rats resulted in the inhibition of plasma DPP-4 with an ED(50) of 0.41 mg/kg. Plasma DPP-4 inhibition was sustained even at 24h after administration of teneligliptin. An oral carbohydrate-loading test in Zucker fatty rats showed that teneligliptin at ≥ 0.1mg/kg increased the maximum increase in plasma glucagon-like peptide-1 and insulin levels, and reduced glucose excursions. This effect was observed over 12h after a dose of 1mg/kg. An oral fat-loading test in Zucker fatty rats also showed that teneligliptin at 1mg/kg reduced triglyceride and free fatty acid excursions. In Zucker fatty rats, repeated administration of teneligliptin for two weeks reduced glucose excursions in the oral carbohydrate-loading test and decreased the plasma levels of triglycerides and free fatty acids under non-fasting conditions. The present studies indicate that teneligliptin is a potent, competitive, and long-lasting DPP-4 inhibitor that improves postprandial hyperglycemia and dyslipidemia by both single and repeated administrations.
authors.affiliation: Department I, Pharmacology Research Laboratories II, Research Division, Mitsubishi Tanabe Pharma Corporation, 2-2-50, Kawagishi, Toda-shi, Saitama 335-8505, Japan. fukuda.sayaka@mu.mt-pharma.co.jp
authors.forename: Sayaka
authors.initials: S
authors.lastname: Fukuda-Tsuru
authors.forename: Jun
authors.initials: J
authors.lastname: Anabuki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Abe
authors.forename: Kumiko
authors.initials: K
authors.lastname: Yoshida
authors.forename: Shinichi
authors.initials: S
authors.lastname: Ishii
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D018819:Dipeptidyl Peptidase 4 / Q000097:blood; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D006943:Hyperglycemia / Q000097:blood / Q000188:drug therapy*; D015228:Hypertriglyceridemia / Q000097:blood / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D008297:Male; D009570:Nitriles / Q000494:pharmacology; D011719:Pyrazines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011924:Rats, Zucker; D000068900:Sitagliptin Phosphate; D053778:Thiazolidines / Q000494:pharmacology / Q000627:therapeutic use*; D014230:Triazoles / Q000494:pharmacology; D000077597:Vildagliptin
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; D000960:Hypolipidemic Agents; D007328:Insulin; D009570:Nitriles; D011719:Pyrazines; D011720:Pyrazoles; D011759:Pyrrolidines; D053778:Thiazolidines; D014230:Triazoles; D052216:Glucagon-Like Peptide 1; D018819:Dipeptidyl Peptidase 4; D000077597:Vildagliptin; D000218:Adamantane; D000068900:Sitagliptin Phosphate