TY - JOUR
T1 - Pharmacology of the glucagon-like peptide-1 analog exenatide extended-release in healthy cats
AU - Rudinsky, A. J.
AU - Adin, C. A.
AU - Borin-Crivellenti, S.
AU - Rajala-Schultz, P.
AU - Hall, M. J.
AU - Gilor, Chen
PY - 2015/4/1
Y1 - 2015/4/1
N2 - 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 (0.13mg/kg) was administered on day 0. Exenatide concentrations were measured for 12wk. A hyperglycemic clamp (target = 225mg/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 1h and 4wk after injection. Comparing clamp I with clamp II, fasting blood glucose decreased (mean ± standard deviation = -11 ± 8mg/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 <50mg/dL increased at 2 and 6wk 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 3wk after a single injection. Further evaluation is needed to determine its safety, efficacy, and duration of action in diabetic cats.
AB - 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 (0.13mg/kg) was administered on day 0. Exenatide concentrations were measured for 12wk. A hyperglycemic clamp (target = 225mg/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 1h and 4wk after injection. Comparing clamp I with clamp II, fasting blood glucose decreased (mean ± standard deviation = -11 ± 8mg/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 <50mg/dL increased at 2 and 6wk 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 3wk after a single injection. Further evaluation is needed to determine its safety, efficacy, and duration of action in diabetic cats.
KW - Diabetes
KW - Exenatide
KW - Feline
KW - Glucagon
KW - Incretin
KW - Insulin
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U2 - 10.1016/j.domaniend.2014.12.003
DO - 10.1016/j.domaniend.2014.12.003
M3 - Article
C2 - 25594949
AN - SCOPUS:84921028458
VL - 51
SP - 78
EP - 85
JO - Domestic Animal Endocrinology
JF - Domestic Animal Endocrinology
SN - 0739-7240
ER -