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1 Diabetes Section, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224; 2 Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada V6T-2B5; and 3 Geriatric Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston Massachusetts 02114
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,
-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 suggest
that, even with this short duration of therapy, exendin-4 treatment had
a significant effect on glucose homeostasis.
insulinotropic effect; glucose disposal; glucagon; C-peptide; hemoglobin A1C
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