A 5-week study of the pharmacokinetics and pharmacodynamics of LY2189265, a novel, long-acting glucagon-like peptide-1 analogue, in patients with type 2 diabetes
A 5-week study of the pharmacokinetics and pharmacodynamics of LY2189265, a novel, long-acting glucagon-like peptide-1 analogue, in patients with type 2 diabetes
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DOI：
10.1111/j.1463-1326.2011.01364.x
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发表时间：
2011-05-01
影响因子：
5.8
通讯作者：
Hardy, T. A.
中科院分区：
文献类型：
--
作者：
Barrington, P.;Chien, J. Y.;Hardy, T. A.
方法：这是一项安慰剂对照、平行组、受试者和研究者盲研究，研究对象（N = 43）为2型糖尿病患者，仅通过饮食和运动或单一口服降糖药进行控制。服用二甲双胍或噻唑烷二酮的受试者继续治疗。接受磺脲、阿卡波糖、瑞格列奈或那格列奈治疗的受试者在入组前改用二甲双胍。受试者每周接受5次剂量，分别为0.05、0.3、1、3、5或8毫克。在空腹和标准测试餐后测定对葡萄糖、胰岛素和c肽浓度的影响。评估LY的药代动力学及其对HBA1c、胰高血糖素、体重、胃排空和安全性参数的影响。结果：每周一次给药，剂量>= 1 mg显著降低空腹血糖、餐后2 h血糖及餐后血糖曲线下面积（AUC） （p < 0.01）。这些效果在第一次给药后就可以看到，并在每周给药周期中持续存在。当葡萄糖AUC正常化时，大多数剂量产生具有统计学意义的胰岛素和c肽AUC增加。除0.3 mg外，所有剂量组的HBA1c均有统计学意义上的降低。最常见的不良反应（ae）是恶心（35例）、头痛（20例）、呕吐（18例）和腹泻（8例）。结论：在2型糖尿病患者中，每周服用一次LY可改善空腹和餐后血糖参数。药代动力学和安全性也支持对这种新型药物的进一步研究。
Methods: This was a placebo-controlled, parallel-group, subject- and investigator-blind study of LY in subjects (N = 43) with type 2 diabetes mellitus controlled with diet and exercise alone or with a single oral antidiabetic medication. Subjects taking metformin or thiazolidinediones continued on their therapy. Subjects receiving sulfonylurea, acarbose, repaglinide or nateglinide were switched to metformin prior to enrollment. Subjects received five once-weekly doses of 0.05, 0.3, 1, 3, 5 or 8 mg. Effects on glucose, insulin and C-peptide concentrations were determined during fasting and following standard test meals. The pharmacokinetics of LY and its effects on HBA1c, glucagon, body weight, gastric emptying and safety parameters were assessed.Results: Once-weekly administration of LY significantly reduced (p < 0.01) fasting plasma glucose, 2-h post-test meal postprandial glucose and area under the curve (AUC) of glucose after test meals at doses >= 1 mg. These effects were seen after the first dose and were sustained through the weekly dosing cycle. Most doses produced statistically significant increases in insulin and C-peptide AUC when normalized for glucose AUC. Statistically significant reductions in HBA1c were observed for all dose groups except 0.3 mg. The most commonly reported adverse effects (AEs) were nausea (35 events), headache (20 events), vomiting (18 events) and diarrhoea (8 events).Conclusions: LY showed improvement in fasting and postprandial glycaemic parameters when administered once weekly in subjects with type 2 diabetes. The pharmacokinetics and safety profiles also support further investigation of this novel agent.