Year: 2015
Type: article
Abstract: Exenatide extended-release (ER) is a microencapsulated formulation of the GLP-1receptor agonist exenatide.It has a protracted pharmacokinetic profile that allows a once-weekly injection with comparable efficacy to insulin and an improved safety profile in type-2 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 weeks.A hyperglycemic clamp (target = 225 mg/dL) was performed on days minus 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 (CGM) was performed on weeks 0, 2 and 6 post-injection.Plasma concentrations of exenatide peaked at 1 hour and 4 weeks post-injection.Comparing Clamp-1 to Clamp-2, fasting BG decreased (mean [±SD] = -11 ± 8 mg/dL, P = 0.02), glucose tolerance improved (median [range] +33% [4-138%], P = 0.04), insulin concentrations increased (+36.5% [-9.9-274.1%],P = 0.02) and glucagon concentrations iii decreased (-4.7% [0-12.1%],P = 0.005).Compared to pre-injection values on CGM, glucose concentrations decreased and the frequency of readings < 50 mg/dL increased at 2 and 6 weeks post-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 weeks after a single injection.Further evaluation is needed to determine its safety, efficacy and duration of action in diabetic cats.
Author: Adam J. Rudinsky
Institution: The Ohio State University
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2617675865