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: 8166983
• 负责人: RICHARD E PRATLEY
• 金额: $ 7.1万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8166983
• 关键词: 2,4-thiazolidinedione; Address; Adipocytes; Affect; Antidiabetic Drugs; Blood Glucose; Blood specimen; Body fat; Bone Density; Brain; 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。 背景：肠促胰岛素激素是由肠道响应食物摄入而产生的激素。 这些激素帮助身体控制葡萄糖（糖）的代谢。 特别是，两种肠促胰岛素激素（GLP-1和GIP）导致胰腺分泌更多的胰岛素以响应高血糖水平。 这有助于身体更有效地代谢葡萄糖，降低血糖水平。 除了对胰腺的影响外，GLP-1和GIP还对其他组织有影响，包括脑、肠道、脂肪细胞和骨骼。 开发用于治疗2型糖尿病（T2 DM）的一类新型口服药物，称为DPP-4抑制剂，通过防止其分解来增加体内GLP-1和GIP活性形式的水平。 这项研究测试了通常用于治疗T2 DM的西格列汀（捷诺维）是否会影响T2 DM患者的骨转换标志物。 研究方法：为了解决这个问题，我们将招募糖尿病通过饮食+运动或二甲双胍（另一种常用于治疗T2 DM的药物）控制的T2 DM患者。 受试者将通过DEXA扫描和3小时混合餐试验测量体脂和骨密度。 在混合餐试验期间，将采集血液样本以测量产生多少GLP-1和GIP。 还将在混合餐试验期间获得的血液样本中测量骨形成标志物。 然后将受试者随机分配至西格列汀（100 mg/天）或匹配安慰剂（不含药物的非活性片剂）治疗8周。 将在开始治疗后4周观察受试者，以评估安全性和耐受性。 治疗8周后，将重复进餐试验。 然后受试者将从其初始治疗（西格列汀或安慰剂）中洗脱1周（即，在此期间他们将不接受研究药物）。 洗脱期后，受试者将开始另一种研究药物的第二个8周治疗期（即，如果受试者最初接受西格列汀治疗，则在第2阶段接受安慰剂治疗，反之亦然）。 在第2阶段结束时，受试者将接受第三次混合餐试验，测量GLP-1、GIP和骨转换标志物。 重要性：最近的研究表明，噻唑烷二酮类口服降糖药物，如罗格列酮（文迪雅）和吡格列酮（Actos），可能会削弱骨骼，增加老年女性糖尿病患者骨折的风险。 拟议的研究将测试DPP-4抑制剂类药物，如西格列汀（捷诺维），是否通过增加GLP-1和GIP的活性对骨转换具有有益作用。 这项初步研究的结果可能表明，需要进行长期研究，以确定DPP-4抑制剂是否能增加糖尿病患者的骨密度并降低骨折风险。