Effects of 1-mo bolus subcutaneous administration of exendin-4 in type 2 diabetes.
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.
Egan
Josephine M
JM
Diabetes Section, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
Meneilly
Graydon S
GS
Elahi
Dariush
D
D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition / Q000187:drug effects; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D000077270:Exenatide; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000494:pharmacology; D015309:Glucose Clamp Technique; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D007515:Islets of Langerhans / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage / Q000627:therapeutic use*; D014688:Venoms
D001786:Blood Glucose; D002096:C-Peptide; D000077270:Exenatide; D005230:Fatty Acids, Nonesterified; D005934:Glucagon; D005947:Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D010455:Peptides; D014688:Venoms