CLINICAL TRIAL: EFFECTS OF 8 WKS TRTMT OF VILDAGLIPTIN,EXENATIDE, OR COMBINATION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 目的：在2型糖尿病患者中，确定8周vildagelatin、艾塞那肽以及vildagelatin+艾塞那肽联合治疗对夜间吸收后期间内源性葡萄糖（RaE）出现率的影响。 研究报告：这项研究将是第一个检查机制，短期治疗与vildagelide和exenelide降低血糖水平的2型糖尿病患者。 我们将研究这些药物对胰岛素、胰高血糖素和游离脂肪酸的影响，以及这些底物的变化如何影响葡萄糖的出现率（血糖的主要决定因素）。 方法：这项单中心研究将采用开放标签、随机设计。 将入组45例健康状况良好的2型糖尿病（HbA 1c 7-10%）男性和女性患者，并随机接受以下三种治疗之一： - vildag 100 mg po qd（两片50 mg片剂） - 艾司那肽5 ug sc bid持续4周，然后10 ug sc持续4周 - vildageles as above + exeneles as above 将采用双示踪法评价患者的葡萄糖利用率。 该测试将在基线和治疗8周后进行两次。 患者将从14：30至08：00接受（3- 3 H）-葡萄糖持续输注。 1800左右，患者将摄入含有（1- 14 C）-葡萄糖的标准餐。 将在整个观察期内采集血样，用于分析葡萄糖、胰高血糖素、胰岛素和其他相关参数。 在8周治疗期间，患者将每两个月随访一次。 临床相关性：Vildagelide和exenelide是FDA批准或FDA正在批准的用于治疗2型糖尿病的新药。 虽然这些化合物的长期治疗已被证明有利于降低空腹血糖和HbA 1c，但迄今为止还没有研究检查这些药物降低血糖的机制。 我们的研究将深入了解这些药物如何影响短期给药后的葡萄糖稳态。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. OBJECTIVE: To determine the effect of 8 weeks treatment of vildagliptin, exenatide and a combination of both vildagliptin plus exenatide on the rate of appearance of endogenous glucose (RaE) during an overnight post-absorptive period in patients with type 2 diabetes. RESEARCH PLAN: This study will be the first to examine the mechanisms by which short-term treatment with vildagliptin and exenatide lower blood glucose levels in type 2 diabetic patients. We will study the effect these drugs have on insulin, glucagon and FFAs and how changes in these substrates influence the rate of glucose appearance (primary determinant of blood glucose). METHODS: This single center study will employ an open label, randomized design. Forty five (45) male and female patients with type 2 diabetes (HbA1c 7-10%), otherwise in good health, will be enrolled and randomized to receive one of the three treatments: - vildagliptin 100 mg po qd (dosed as two 50mg tablets) - exenatide 5 ug sc bid for 4 wk, then 10 ug sc for 4 wk - vildagliptin as above + exenatide as above A double tracer method will be employed to evaluate glucose utilization by the patients. The test will be conducted twice, at baseline and after 8 weeks of treatment. Patients will receive a continuous infusion of (3-3H) - glucose from 1430 until 0800. Around 1800 the patient will ingest a standardized meal containing (1-14C)-glucose. Blood samples will be taken throughout observation period for analysis of glucose, glucagon, insulin, and other relevant parameters. During the 8 week treatment patients will be followed up bimonthly. CLINICAL RELEVANCE: Vildagliptin and exenatide are new drugs approved by FDA (exenatide) or in process of approval by the FDA (vildagliptin) for the treatment of type 2 diabetes. Although long term treatment with these compounds has been shown beneficial in reducing both fasting plasma glucose and HbA1c, no studies to date have examined the mechanisms by which these drugs lower blood glucose. Our study will give an insight on how these drugs affect glucose homeostasis after short term administration.