Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Diabetes Obes Metab. 2014 May;16(5):451-6. doi: 10.1111/dom.12240. Epub 2013 Dec 10.
Any differences observed between natural glucagon-like peptide-1 (GLP-1) and studies obtained with analogues might call for renewed considerations concerning the use and design of such analogues. Thus, we aimed to evaluate the dose-response relationship of recombinant glucagon-like peptide-1 (7-36) amide (rGLP-1) administered by continuous subcutaneous infusion (CSCI) in subjects with type 2 diabetes.
We compared the efficacy and safety of three doses of recombinant GLP-1, ranging from 1.25 to 5.0 pmol/kg/min (pkm) and placebo, given by continuous subcutaneous infusion over 3 months in combination with metformin and sulphonylurea (SU), to lower haemoglobin A1c (HbA1c), fasting plasma glucose and weight in 95 type 2 diabetes patients with inadequate glycaemic control.
The mean decreases in HbA1c at endpoint (week 12) were significantly greater for all three rGLP-1 dose groups when each was compared with the placebo group, with the greatest decrease occurring in the 5.0 pkm dose group (-1.3%, s.d. ± 0.18, p < 0.001). The mean decreases in fasting plasma glucose from baseline to endpoint were significantly greater for all three rGLP-1 dose groups than for the placebo group, with the greatest decrease occurring in the 5.0 pkm dose group (-26.0 mg/dl, s.d. ± 8.5, p = 0.02). Body weight was significantly reduced by 1.8 kg (s.d. ± 1.3) in the 1.25 pkm dose group only (p = 0.04).
Administration of rGLP-1 by CSCI over a 12-week period in combination with metformin and an SU had a dose dependent effect in lowering HbA1c and fasting plasma glucose. However, administration of rGLP-1 by CSCI may be less effective with respect to lowering of body weight compared with the daily and once weekly analogues.
天然胰高血糖素样肽-1（GLP-1）与类似物研究之间观察到的任何差异都可能需要重新考虑此类类似物的使用和设计。因此，我们旨在评估通过连续皮下输注（CSCI）给予重组 GLP-1（7-36）酰胺（rGLP-1）的剂量反应关系，该药物在 2 型糖尿病患者中使用，以降低糖化血红蛋白（HbA1c）、空腹血糖和体重。
我们比较了三种剂量的重组 GLP-1（1.25 至 5.0pmol/kg/min[pkm]）和安慰剂，在 3 个月内与二甲双胍和磺酰脲（SU）联合通过连续皮下输注给药，以降低 95 例血糖控制不佳的 2 型糖尿病患者的糖化血红蛋白（HbA1c）、空腹血糖和体重。
与安慰剂组相比，所有三个 rGLP-1 剂量组在终点（第 12 周）的 HbA1c 平均下降均显著更大，其中最大下降发生在 5.0pkm 剂量组（-1.3%，s.d.±0.18，p<0.001）。与安慰剂组相比，所有三个 rGLP-1 剂量组的空腹血糖从基线到终点的平均下降均显著更大，其中最大下降发生在 5.0pkm 剂量组（-26.0mg/dl，s.d.±8.5，p=0.02）。仅在 1.25pkm 剂量组体重显著减轻 1.8kg（s.d.±1.3）（p=0.04）。
在 12 周内通过 CSCI 给予 rGLP-1 与二甲双胍和 SU 联合使用具有剂量依赖性降低 HbA1c 和空腹血糖的作用。然而，与每日和每周一次的类似物相比，通过 CSCI 给予 rGLP-1 可能在降低体重方面效果较差。
