1. Effects of 1-mo bolus subcutaneous administration of exendin-4 in type 2 diabetes.
- Author
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Egan JM, Meneilly GS, and Elahi D
- Subjects
- Aged, Blood Glucose metabolism, Body Composition drug effects, C-Peptide blood, Diabetes Mellitus, Type 2 blood, Exenatide, Fatty Acids, Nonesterified blood, Female, Glucagon blood, Glucose pharmacology, Glucose Clamp Technique, Glycated Hemoglobin metabolism, Humans, Hypoglycemic Agents administration & dosage, Injections, Subcutaneous, Insulin blood, Insulin Resistance physiology, Islets of Langerhans drug effects, Male, Middle Aged, Peptides administration & dosage, Diabetes Mellitus, Type 2 drug therapy, Hypoglycemic Agents therapeutic use, Peptides therapeutic use, Venoms
- Abstract
A gut insulinotropic peptide, glucagon-like peptide-1 (GLP-1), when given continuously subcutaneously, has been shown to be an effective agent to treat type 2 diabetes. Because of inactivation by dipeptidyl peptidase IV (DPP IV), it has a very short half-life (90-120 s), hence the need for continuous administration. Exendin-4 is an agonist of the GLP-1 receptor. It is not a substrate for DPP IV, and we previously demonstrated that intravenous administration has potent insulinotropic properties in type 2 diabetic volunteers. We evaluated the efficacy of bolus subcutaneous exendin-4 in insulin-naive type 2 diabetic volunteers. Ten patients aged 44-72 yr with mean fasting glucose levels of 11.4 +/- 0.9 mmol/l were enrolled, and daily or twice-daily bolus subcutaneous exendin-4 was self-administered for 1 mo. Glycosylated hemoglobin, multiple daily capillary blood glucose, beta-cell sensitivity to glucose, and peripheral tissue sensitivity to insulin were compared before and after treatment. The greatest decline in capillary blood glucose was seen before bed, with a drop from 15.5 to 9.2 mmol/l (P < 0.0001). Glycosylated hemoglobin improved significantly with treatment, from 9.1 to 8.3% (P = 0.009). beta-Cell sensitivity to glucose was improved, as assessed by C-peptide levels during a hyperglycemic clamp. No significant adverse effects were noted or reported. Our data suggest that, even with this short duration of therapy, exendin-4 treatment had a significant effect on glucose homeostasis.
- Published
- 2003
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