title: Effect of linagliptin, alone and in combination with voglibose or exendin-4, on glucose control in male ZDF rats.
abstract: The effects of the dipeptidyl peptidase-4 (DPP-4) inhibitor, linagliptin, alone and in combination with voglibose or exendin-4, on glycaemic control and body weight were assessed in an animal model of type 2 diabetes. Voglibose is an α-glucosidase inhibitor but also increases glucagon-like peptide 1 (GLP-1). Exendin-4 is a GLP-1 receptor agonist. Male Zucker Diabetic Fatty (ZDF) rats were dosed for 3 days, fasted overnight and a sucrose/glucose tolerance test was performed. Linagliptin (1mg/kg po) improved glucose tolerance by increasing plasma GLP-1 (active) and insulin secretion, whilst having no effect on body weight. Voglibose (1 and 10mg/kg po) reduced body weight, improved glycaemic control, reduced plasma insulin and increased total but not active GLP-1. The combination of linagliptin and voglibose significantly reduced body weight, improved glycaemic control and reduced plasma insulin compared to linagliptin alone. Furthermore, linagliptin plus voglibose produced a marked increase in GLP-1 (active) at 5min post-sucrose, compared to linagliptin, possibly because linagliptin prevented the degradation of GLP-1 secreted in response to voglibose. Exendin-4 (10μg/kg sc) significantly reduced body weight, improved glucose tolerance but reduced GLP-1 (active). The combination of linagliptin and exendin-4 significantly reduced body weight and improved glycaemic control but had no effect on plasma GLP-1. Overall it did not markedly improve glycaemic control compared to the individual drugs. The improved glucose control, reduced body weight and markedly increased plasma GLP-1 levels in animals given linagliptin with voglibose, suggests that this combination may be particularly beneficial in the treatment of type 2 diabetes.
authors: RenaSci Limited, BioCity, Pennyfoot Street, Nottingham NG1 1GF, UK.
authors: Robert B
authors: RB
authors: Jones
authors: RenaSci Limited, BioCity, Pennyfoot Street, Nottingham NG1 1GF, UK.
authors: Steven P
authors: SP
authors: Vickers
authors: RenaSci Limited, BioCity, Pennyfoot Street, Nottingham NG1 1GF, UK. Electronic address: sharon.cheetham@renasci.co.uk.
authors: Sharon C
authors: SC
authors: Cheetham
authors: RenaSci Limited, BioCity, Pennyfoot Street, Nottingham NG1 1GF, UK.
authors: Katie R
authors: KR
authors: Headland
authors: Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany.
authors: Michael
authors: M
authors: Mark
authors: Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany.
authors: Thomas
authors: T
authors: Klein
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D000077270:Exenatide; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007294:Inositol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000069476:Linagliptin; D008297:Male; D010455:Peptides / Q000008:administration & dosage*; D011687:Purines / Q000008:administration & dosage*; D011799:Quinazolines / Q000008:administration & dosage*; D051381:Rats; D011924:Rats, Zucker; D016896:Treatment Outcome; D014688:Venoms / Q000008:administration & dosage*
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D010455:Peptides; D011687:Purines; D011799:Quinazolines; D014688:Venoms; D000069476:Linagliptin; D007294:Inositol; D000077270:Exenatide; C102817:voglibose
keywords: Exendin-4; Exendin-4 (PubChem CID: 16157882); GLP-1; Glucose control; Linagliptin; Linagliptin (PubChem CID:10096344); Type 2 diabetes; Voglibose; Voglibose (PubChem CID: 444020)