title: Pharmacology of the glucagon-like peptide-1 analog exenatide extended-release in healthy cats.
abstract: Exenatide extended-release (ER) is a microencapsulated formulation of the glucagon-like peptide 1-receptor agonist exenatide. It has a protracted pharmacokinetic profile that allows a once-weekly injection with comparable efficacy to insulin with an improved safety profile in type II diabetic people. Here, we studied the pharmacology of exenatide ER in 6 healthy cats. A single subcutaneous injection of exenatide ER (0.13 mg/kg) was administered on day 0. Exenatide concentrations were measured for 12 wk. A hyperglycemic clamp (target = 225 mg/dL) was performed on days -7 (clamp I) and 21 (clamp II) with measurements of insulin and glucagon concentrations. Glucose tolerance was defined as the amount of glucose required to maintain hyperglycemia during the clamp. Continuous glucose monitoring was performed on weeks 0, 2, and 6 after injection. Plasma concentrations of exenatide peaked at 1 h and 4 wk after injection. Comparing clamp I with clamp II, fasting blood glucose decreased (mean ± standard deviation = -11 ± 8 mg/dL, P = 0.02), glucose tolerance improved (median [range] +33% [4%-138%], P = 0.04), insulin concentrations increased (+36.5% [-9.9% to 274.1%], P = 0.02), and glucagon concentrations decreased (-4.7% [0%-12.1%], P = 0.005). Compared with preinjection values on continuous glucose monitoring, glucose concentrations decreased and the frequency of readings <50 mg/dL increased at 2 and 6 wk after injection of exenatide ER. This did not correspond to clinical hypoglycemia. No other side effects were observed throughout the study. Exenatide ER was safe and effective in improving glucose tolerance 3 wk after a single injection. Further evaluation is needed to determine its safety, efficacy, and duration of action in diabetic cats.
authors.affiliation: Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Rudinsky
authors.affiliation: Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Adin
authors.affiliation: FAPESP (#2013/00027-6) and FCAV, Universidade Estadual Paulista (UNESP), Jaboticabal, Sao Paulo, Brazil.
authors.forename: S
authors.initials: S
authors.lastname: Borin-Crivellenti
authors.affiliation: Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: P
authors.initials: P
authors.lastname: Rajala-Schultz
authors.affiliation: Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Hall
authors.affiliation: Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA. Electronic address: gilor.1@osu.edu.
authors.forename: C
authors.initials: C
authors.lastname: Gilor
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002371:Cat Diseases / Q000188:drug therapy*; D002415:Cats; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000662:veterinary*; D004357:Drug Synergism; D000077270:Exenatide; D005215:Fasting; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives*; D015309:Glucose Clamp Technique; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D007328:Insulin / Q000097:blood; D008863:Microspheres; D010455:Peptides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D014688:Venoms / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010455:Peptides; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D000077270:Exenatide; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
keywords: Diabetes; Exenatide; Feline; Glucagon; Incretin; Insulin