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

点击翻译按钮获取中文摘要

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.