在磺脲类药物控制不良的2型糖尿病患者，胰高血糖素样肽1输注必须保持每天24小时才能将血糖控制良好

Glucagon-Like Peptide-1 Infusion Must Be Maintained for 24 h/day to Obtain Acceptable Glycemia in Type 2 Diabetic Patients Who Are Poorly Controlled on Sulphonylurea Treatment

Abstract 2001年

在磺脲类药物控制不良的2型糖尿病患者，胰高血糖素样肽1输注必须保持每天24小时才能将血糖控制良好海南医学院附属医院内分泌科王新军

OBJECTIVE?To assess the efficacy and safety of glucagon-like peptide-1 (GLP-1) on the plasma glucose level when given as a continuous infusion for either 16 or 24 h per day to type 2 diabetic patients who were poorly controlled on sulfonylurea treatment.

评估胰高血糖素样肽1（GLP - 1）连续皮下输注每天16或24小时对磺脲类血糖控制不良的2型糖尿病患者血糖水平的疗效和安全性。

RESEARCH DESIGN AND METHODS?This single-center, randomized, parallel, double-blind, placebo-controlled trial was conducted in 40 hospitalized patients who were randomized to receive infusions of either placebo or GLP-1 4 or 8 ng ? kg^?1 ? min^?1 for either 16 or 24 h per day for 7 days. At predetermined intervals, 24-h profiles of glucose, glucagon, and insulin were measured. Adverse events and clinical chemistry and hematology were recorded.

研究设计和方法：这是一项单中心、随机、平行、双盲、安慰剂对照试验，共纳入40例住院的患者，随机接受安慰剂、4或8 ng ? kg^?1 ? min^?1GLP - 1输注16或24小时，共7天。在预定的时间，测量24小时血糖、胰高血糖素和胰岛素谱。记录不良事件和临床生化和血液学数据。

RESULTS?For all active treatment groups, the change in average glucose (area under the curve [AUC] for day 7 minus AUC for day 0 divided by 24 h) was statistically significantly different from placebo (P ≤ 0.001). The GLP-1 8 ng ? kg^?1 ? min^?1 dose given for 24 h was more efficacious than any of the other doses (P ≤ 0.05). Nocturnal and fasting plasma glucose levels at day 7 were greater in the 16-h groups compared with the 24-h groups (P ≤ 0.05). Insulin AUC did not show any treatment effect for any of the treatment groups when change was assessed from day 0 to day 7. However, for the 16-h groups, the pattern of the insulin profiles changed; the insulin profiles were considerably higher during the initial 3?4 h after restart of the GLP-1 infusion on day 7, although there was a tendency for insulin levels to decrease during the afternoon and evening. Glucagon AUC decreased significantly for all active treatment groups compared with placebo. GLP-1 was generally well tolerated.

结果：治疗组平均血糖的变化（第7天曲线下面积[AUC]减第0天AUC除以24小时）与安慰剂组相比有统计学显著差异（P≤0.001）。 GLP ? 1组24小时8 ng ? kg^?1 ? min^?1的剂量比任何其他剂量（P≤0.05）更有效。 与24小时组相比，16小时组第7天夜间和空腹血糖水平较高（P≤0.05）。治疗组胰岛素的AUC从第0天到第7天没有表现出任何治疗效果的变化是。然而，在16 h组，胰岛素谱的方式可见变化；在第7天重新输注GLP ? 1后3～4小时，胰岛素谱明显升高，下午和晚上胰岛素水平有降低的趋势。与安慰剂组相比，所有治疗组胰高血糖素的AUC显着下降。 GLP - 1一般耐受良好。
CONCLUSIONS?This study demonstrated that GLP-1 should be given continuously to obtain the most optimal glycemic control. Because of the short plasma half-life of native GLP-1, long-acting derivatives should be developed to make GLP-1 treatment clinically relevant.

结论：本研究显示，GLP - 1应连续给药，以获得最优化的血糖控制。因为天然GLP - 1的血浆半衰期较短，应研发GLP - 1长效衍生物用于临床。