Glycemia Reduction Approaches in Diabetes: A comparative effectiveness study

糖尿病的降血糖方法：比较有效性研究

基本信息

批准号：
8549237
负责人：
JOHN M LACHIN
金额：
$ 2596.34万
依托单位：
GEORGE WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-25 至 2017-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8549237
关键词：
Address Adverse effects Affect Agonist Amputation Beta Cell Blindness Cardiovascular Diseases Cell physiology Cessation of life Characteristics Chronic Disease Clinical Trials Combination Medication Complications of Diabetes Mellitus Conflict (Psychology)Data Development Diabetes Mellitus Diabetic Angiopathies Disease Drug Combinations Effectiveness Enrollment Epidemic Evaluation Failure Glimepiride Glucose Glycosylated hemoglobin A Goals Guidelines Human Hypoglycemia Incidence Insulin Investigation Kidney Diseases Kidney Failure Laboratories Living Costs Metabolic Metabolic Control Metabolism Metformin Microalbuminuria Neuropathy New Agents Non-Insulin-Dependent Diabetes Mellitus Outcome Participant Patients Persons Pharmaceutical Preparations Population Positioning Attribute Prevalence Public Health Quality of life Randomized Regimen Relative (related person)Research Retinal Diseases Risk Risk Factors Secondary to Site Sulfonylurea Compounds Time Weight Gain Work basal insulin cardiovascular disorder risk comparative effectiveness cost effectiveness diabetic economic cost effectiveness clinical trial effectiveness research glargine glucagon-like peptide 1 improved inhibitor/antagonist liraglutide premature prevent primary outcome public health relevance response success

项目摘要

DESCRIPTION (provided by applicant): The epidemic of type 2 diabetes (T2DM) that has affected the world's populations threatens to become this century's major public health problem. The enormous human and economic costs associated with the epidemic in the US (prevalence of ~25 million, incidence 1.9 million per year) are related primarily to the development of long-term complications including retinopathy, nephropathy, and neuropathy that cause more cases of blindness, renal failure, and amputations than any other disease. Cardiovascular disease (CVD) is increased 2-5 fold in T2DM and is the leading cause of premature death. High quality clinical trials have established the importance of lowering glycemia to reduce long-term complications. Progression of T2DM usually requires addition of a second agent to metformin, the accepted first line treatment. With the development of numerous new classes of glucose-lowering drugs, evidence to guide the choice of the second agent is lacking, prompting the proliferation of conflicting guidelines that acknowledge this deficiency. Moreover, while these agents are typically used for many years, data on long-term use are non-existent. Comparative effectiveness research is a high priority to improve public health and maximize cost-effectiveness in the treatment of T2DM. In addition, efforts to individualize T2DM therapy and determine whether selected therapies work better in some patients than others are needed, as are studies to understand differential effects of various therapies on metabolism over time. The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study will address these questions in a randomized, pragmatic clinical trial in 6000 patients with recent-onset (<5 years duration) T2DM. GRADE will compare the metabolic effects of four common glucose-lowering medications, the sulfonylurea glimepiride, DPP-4 inhibitor sitagliptin, GLP-1 agonist liraglutide, and basal insulin glargine, added to metformin, over a clinically meaningful duration, with a mean exposure of 4.5 (3-6) years. The primary outcome is the time to primary metabolic failure (hemoglobin A1c (A1C)>7%, subsequently confirmed).Other outcomes include mean A1C; time to a secondary metabolic outcome of A1C>7.5%, confirmed, after which basal insulin "rescue" therapy will be added; and adverse effects such as weight gain and hypoglycemia, effects on selected microvascular disease and CVD risk factors, tolerability and quality-of-life, and cost and cost-effectiveness. We will also examine the phenotypic characteristics and pathophysiologic factors associated with metabolic response to and/or failure of the drug combinations.

描述（由申请人提供）：2 型糖尿病（T2DM）的流行已经影响了世界人口，有可能成为本世纪的主要公共卫生问题。在美国，与该流行病相关的巨大人力和经济成本（患病率约为 2500 万，每年发病率 190 万）主要与长期并发症的发生有关，包括视网膜病、肾病和神经病，这些并发症会导致更多失明病例、肾衰竭和截肢比任何其他疾病都多。心血管疾病 (CVD) 在 T2DM 中增加 2-5 倍，是过早死亡的主要原因。高质量的临床试验已经证实降低血糖对于减少长期并发症的重要性。 T2DM 的进展通常需要在二甲双胍（公认的一线治疗）的基础上添加第二种药物。随着众多新型降糖药物的开发，缺乏指导第二种药物选择的证据，导致承认这一缺陷的相互矛盾的指南激增。此外，虽然这些药物通常使用多年，但不存在长期使用的数据。比较有效性研究是改善公众健康和最大限度提高 T2DM 治疗成本效益的首要任务。此外，还需要努力使 T2DM 治疗个体化，并确定所选疗法在某些患者中是否比其他患者效果更好，还需要开展研究来了解不同疗法随时间推移对代谢的不同影响。糖尿病降血糖方法：比较有效性 (GRADE) 研究将在一项随机、实用的临床试验中解决这些问题，该试验对 6000 名新发（病程<5 年）T2DM 患者进行。 GRADE 将比较四种常见降糖药物（磺酰脲类格列美脲、DPP-4 抑制剂西他列汀、GLP-1 激动剂利拉鲁肽和基础甘精胰岛素）在有临床意义的持续时间内添加到二甲双胍中的代谢影响，平均暴露量为4.5（3-6）年。主要结果是原发性代谢衰竭的时间（血红蛋白 A1c (A1C)>7%，随后得到证实）。其他结果包括平均 A1C；确认达到 A1C>7.5% 次要代谢结果的时间，之后将添加基础胰岛素“救援”治疗；体重增加和低血糖等不良反应、对特定微血管疾病和 CVD 危险因素的影响、耐受性和生活质量以及成本和成本效益。我们还将检查与药物组合的代谢反应和/或失败相关的表型特征和病理生理因素。