CLINICAL TRIAL: EFFECTS OF SITAGLIPTIN ON BONE TURNOVER IN PTS WITH TYPE 2 DIABE

临床试验：西他列汀对 2 型糖尿病患者骨转换的影响

• 批准号: 7952124
• 负责人: RICHARD E PRATLEY
• 金额: $ 2.15万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7952124
• 关键词: 2,4-thiazolidinedione; Address; Adipocytes; Affect; Antidiabetic Drugs; Blood Glucose; Blood specimen; Body fat; Bone Density; Brain; Clinical Research; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; DEXA; Diabetes Mellitus; Eating; Fracture; Funding; GNAI2 gene; Glucose; Grant; Hormones; Hour; Institution; Insulin; Longitudinal Studies; Measurement; Measures; Medicine; Metformin; Methods; Non-Insulin-Dependent Diabetes Mellitus; Oral; Osteogenesis; Pancreas; Patients; Pharmaceutical Preparations; Pilot Projects; Pioglitazone; Placebos; Randomized; Recruitment Activity; Research; Research Personnel; Resources; Risk; Safety; Scanning; Source; Tablets; Takeda brand of pioglitazone hydrochloride; Testing; Thiazolidinediones; Tissues; United States National Institutes of Health; bone; bone turnover; diet and exercise; glucagon-like peptide 1; glucose metabolism; incretin hormone; inhibitor/antagonist; older women; prevent; response; rosiglitazone; sugar; treatment duration

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. Background: Incretin hormones are hormones produced by the gut in response to food intake. These hormones help the body to control the metabolism of glucose (sugar). In particular, two incretin hormones (GLP-1 and GIP) cause the pancreas to secrete more insulin in response to high blood glucose levels. This helps the body to metabolize the glucose more effectively, lowering blood sugar levels. In addition to their effects on the pancreas, GLP-1 and GIP have effects on other tissues, including the brain, gut, fat cells and bone. A new class of oral drugs developed for the treatment of type 2 diabetes mellitus (T2DM) called DPP-4 inhibitors increases levels of the active forms of GLP-1 and GIP in the body by preventing their breakdown. This study tests whether a medicine in this class called sitagliptin (Januvia), which is commonly used to treat T2DM, affects markers of bone turnover in patients with T2DM. Methods: To address this question, we will recruit patients with T2DM whose diabetes is controlled either diet+exercise or with metformin (another medicine commonly used to treat T2DM). Subjects will undergo measurement of body fat and bone mineral density by DEXA scanning and a 3-hour mixed meal test. During the mixed meal test, blood samples will be taken to measure how much GLP-1 and GIP are produced. Markers of bone formation will also be measured in blood samples obtained during the mixed meal test. Subjects will then be randomly assigned to 8 weeks of treatment with either sitagliptin (100 mg/day) or matching placebo (an inactive tablet that does not contain medication). Subjects will be seen 4 weeks after commencing treatment to assess safety and tolerability. After 8 weeks of treatment, the meal test will be repeated. Subjects will then be washed off of their initial treatment (sitagliptin or placebo) for 1 week (that is, they will receive no study medication during this period). After the washout period, they will commence a second 8 week period of treatment with the other study medication (that is, if they received sitagliptin initially, they will receive placebo during period 2 and vice versa). At the end of period 2, subjects will undergo a third mixed meal test with measurement of GLP-1, GIP and markers of bone turnover. Significance: Recent studies suggest that oral antidiabetic medications of the thiazolidinedione class such as rosiglitazone (Avandia) and pioglitazone (Actos), may weaken bones, increasing the risk of fractures in older women with diabetes. The proposed study will test whether drugs of the DPP-4 inhibitor class, such as sitagliptin (Januvia), have beneficial effects on bone turnover by increasing the activity of GLP-1 and GIP. Results of this pilot study may suggest the need to perform longer-term studies to determine whether DPP-4 inhibitors increase bone mineral density and reduce the risk of fractures in patients with diabetes.

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。 背景：胰岛素激素是肠道对食物摄入的反应而产生的激素。这些激素帮助身体控制葡萄糖(糖)的新陈代谢。特别值得一提的是，两种胰岛素激素(GLP-1和GIP)会导致胰腺在高血糖时分泌更多的胰岛素。这有助于身体更有效地代谢葡萄糖，从而降低血糖水平。除了对胰腺的影响外，GLP-1和GIP对其他组织也有影响，包括大脑、肠道、脂肪细胞和骨骼。一种新开发的治疗2型糖尿病(T2 DM)的口服药物被称为DPP-4抑制剂，它通过防止GLP-1和GIP的分解来提高它们在体内的活性形式的水平。这项研究测试了一种名为西格列汀(Januvia)的此类药物，它通常用于治疗T2 DM，是否会影响T2 DM患者的骨转换标志。 方法：为了解决这个问题，我们将招募糖尿病控制在饮食+运动或二甲双胍(另一种治疗T2 DM的药物)的T2 DM患者。受试者将通过DEXA扫描和3小时的混合餐测试来测量体脂和骨密度。在混合餐测试期间，将采集血样以测量产生多少GLP-1和GIP。在混合餐测试期间采集的血液样本中也将测量骨形成的标志。然后，受试者将被随机分配到为期8周的治疗中，服用西格列汀(每天100毫克)或匹配的安慰剂(一种不含药物的非活性片剂)。受试者将在开始治疗4周后接受检查，以评估安全性和耐受性。治疗8周后，复查膳食试验。然后，受试者将在一周内停止最初的治疗(西格列汀或安慰剂)(即在此期间，他们将不接受任何研究药物)。洗脱期结束后，他们将开始第二个8周的疗程，使用其他研究药物(即，如果他们最初接受西格列汀治疗，他们将在第二阶段接受安慰剂治疗，反之亦然)。在第二阶段结束时，受试者将接受第三次混合餐测试，测量GLP-1、GIP和骨转换标志物。 意义：最近的研究表明，口服噻唑烷二酮类药物，如罗格列酮(文迪雅)和吡格列酮(Actos)，可能会削弱骨骼，增加老年糖尿病女性骨折的风险。这项拟议的研究将测试DPP-4抑制剂类药物，如西格列汀(Januvia)，是否通过增加GLP-1和GIP的活性来改善骨转换。这项先导性研究的结果可能表明有必要进行更长期的研究，以确定DPP-4抑制剂是否增加糖尿病患者的骨密度并降低骨折的风险。