口服药物治疗及进展 北京煤炭总医院 内分泌科 李洪梅.ppt

[486-P] The Long-Acting GLP-1 Derivative, NN2211, Restores Beta Cell Sensitivity to Glucose in Subjects with Type 2 Diabetes ANNETTE M. CHANG, GRETHE JAKOBSEN, JEPPE STURIS, BOB AN, MARLA J. SMITH, CATHIE J. BLOEM, ANDRZEJ GALECKI, JEFFREY B. HALTER. Ann Arbor, MI; Bagsvaerd, Denmark; Princeton, NJ. Saturday, June 14, 2003, 5:00 PM, Poster Presentation: Clinical Therapeutics/New Technology - Pharmacologic Treatment of Diabetes or its Complications (5:00 PM - 6:00 PM) Glucagon-like peptide 1 (GLP-1) glucose-dependently stimulates insulin secretion, but its very short half-life limits its use as a therapeutic agent. NN2211 is a long-acting GLP-1 derivative suitable for once-daily administration. We tested the effect of NN2211 on beta cell sensitivity in 10 subjects with type 2 diabetes, age 63 ?8 years (mean ?SD), BMI 30.1 ?4.2 kg/m? HbA1C 6.5 ?0.8%, in a randomized, double-blind, placebo-controlled, crossover study. A single subcutaneous injection of NN2211 (7.5 μg/kg) or placebo was administered in random order to subjects with type 2 diabetes 9 hours (equal to reported t-max) prior to testing. Beta cell sensitivity was assessed by a graded glucose infusion protocol with plasma glucose levels matched over the range of 5 to 12 mmol/L. Insulin secretion rates (ISR) were estimated by deconvolution of circulating C-peptide concentrations. Findings were also compared to responses of 10 healthy, nondiabetic volunteers to the same glucose infusion protocol. Compared to placebo, a single dose of NN2211 increased insulin and C-peptide levels, increased ISR area under the curve (AUC) (1130 ?150 vs. 668 ?106 pmol/min*kg; p 0.001), and increased slope of ISR vs. plasma glucose (1.26 ?0.36 vs. 0.54 ?0.18 pmol*L/(min*mmol*kg); p 0.014), to values similar to nondiabetic controls who did not receive the drug (ISR AUC 1206 ?99; slope of ISR vs. plasma glucose 1.44 ?0.18). Insulin clearance and glucagon AUC were not significantly different between placebo treatment, NN2211 trea