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利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 目的：观察维格列汀、艾塞那肽及维达格列汀联合艾塞那肽治疗8周对2型糖尿病患者吸收后夜间内源性血糖(RAE)发生率的影响。 研究计划：这项研究将首次研究维达格列汀和艾塞那汀短期治疗降低2型糖尿病患者血糖水平的机制。我们将研究这些药物对胰岛素、胰升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出现的比率(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。45(45)名男性和女性2型糖尿病患者(HbA1c 7%-10%)，其他健康状况良好，将被纳入并随机接受三种治疗之一： -维格列汀100毫克，口服，每日一次(分两片50毫克) -exenatide 5 ug sc，竞标4周，然后10 ug sc，4周 -VILDAGLIPTIN如上+艾塞那肽如上 将采用双示踪法评估患者的葡萄糖利用情况。这项测试将在基线和治疗8周后进行两次。从14点30分到8点，患者将接受(3-3H)-葡萄糖的持续输注。大约1800岁左右，患者将摄入一份含有(1-14C)-葡萄糖的标准膳食。在整个观察期内采集血样，分析血糖、胰升糖素、胰岛素和其他相关参数。在8周的治疗期间，患者将每两个月进行一次随访。 临床意义：维拉格列汀和埃塞那肽是FDA批准或正在审批中的治疗2型糖尿病的新药。虽然这些化合物的长期治疗被证明对降低空腹血糖和糖化血红蛋白都有好处，但到目前为止还没有研究检验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在短期给药后如何影响血糖稳态。

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.