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Articles in PresS, published online ahead of print December 10, 2002
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00315.2002
Submitted on July 15, 2002
Accepted on November 27, 2002
1 Diabetes Section, NIA, NIH, Baltimore, MD, USA
2 Department of Medicine, University of British Columbia, Vancouver, BC, Canada
3 Geriatric Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
* To whom correspondence should be addressed. E-mail: delahi{at}partners.org.
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. Due to inactivation by dipeptidyl peptidase IV (DPP 1V), it has a very short half-life (90-120 seconds): hence the need for continuous administration. Exendin-4 is an agonist of the GLP-1 receptor. It is not a substrate for DPP 1V 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 age 44 to 72 years with mean fasting glucose levels 11.4 ±0.9 mmol/l were enrolled and daily or twice daily bolus subcutaneous exendin-4 was self-administered for one month. Glycosylated hemoglobin, multiple daily capillary blood glucose, 
-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). -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 suggests that even with this short duration of therapy, exendin-4 treatment had a significant effect on glucose homeostasis.
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