ADMINISTRATION OF GLP 1 BY SUBCUTANEOUS DELIVERY--DETERMINATION OF DOSE

$575M01FY2000RRNIH

Massachusetts General Hospital, Boston MA

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Abstract

To determine the dose and efficacy of GLP-1, 7-36 amide, delivered as a continuous subcutaneous infusion by external pump, that improves blood glucose profiles maximally. The range of doses will be selected to bracket those necessary to achieve a plasma level of approximately 100 pmol/L, which has been demonstrated in previous studies to provide a glucose lowering effect. In addition, we will determine which dose, if any, is associated with adverse side-effects (predominantly gastrointestinal). In addition to blood glucose, insulin, glucagon, and GLP-1 levels will be measured to examine the efficacy of GLP-1 administered continuously to improve metabolism in Type 2 diabetes. The first four subjects have been studied. GLP infusion at all 3 doses (maximum 0.4 mol/kg/hr) was tolerated without adverse effects. Average blood glucose levels decreased by approximately 20% with plasma levels of GLP in the 50-150 pmol/l range. A publication is in preparation.

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