Continuation of the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study

糖尿病降血糖方法的延续：比较有效性 (GRADE) 研究

基本信息

批准号：
10018856
负责人：
JOHN M LACHIN
金额：
$ 718.33万
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 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10018856
关键词：
Address Adherence Adverse effects Affect Agonist Amputation Antidiabetic Drugs Beta Cell Blindness Cardiovascular Diseases Cell physiology Cessation of life Characteristics Chronic Disease Clinical Clinical Trials Combination Medication Comparative Effectiveness Research Complications of Diabetes Mellitus Conflict (Psychology)Consensus Data Development Diabetes Mellitus Diagnosis Disease Drug Combinations Enrollment Epidemic Evaluation Failure Glimepiride Glucose Glycosylated hemoglobin A Goals Guidelines Human Hypoglycemia Incidence Insulin Investigation Kidney Diseases Kidney Failure Laboratories Metabolic Metabolic Control Metabolism Metformin Microalbuminuria Microvascular Dysfunction Neuropathy New Agents Non-Insulin-Dependent Diabetes Mellitus Outcome Participant Patients Persons Pharmaceutical Preparations Phenotype Population Positioning Attribute Pragmatic clinical trial Predictive Factor Prevalence Protocols documentation Public Health Quality of life Randomized Regimen Research Retinal Diseases Risk Risk Factors Secondary to Site Sulfonylurea Compounds Time Weight Gain Work basal insulin cardiovascular disorder risk comparative effectiveness cost effectiveness diabetes mellitus therapy economic cost effectiveness clinical trial follow-up glargine glucagon-like peptide 1 improved inhibitor/antagonist liraglutide premature prevent primary outcome recruit relative effectiveness response success

Address Adherence Adverse effects Affect Agonist Amputation Antidiabetic Drugs Beta Cell Blindness Cardiovascular Diseases Cell physiology Cessation of life Characteristics Chronic Disease Clinical Clinical Trials Combination Medication Comparative Effectiveness Research Complications of Diabetes Mellitus Conflict (Psychology)Consensus Data Development Diabetes Mellitus Diagnosis Disease Drug Combinations Enrollment Epidemic Evaluation Failure Glimepiride Glucose Glycosylated hemoglobin A Goals Guidelines Human Hypoglycemia Incidence Insulin Investigation Kidney Diseases Kidney Failure Laboratories Metabolic Metabolic Control Metabolism Metformin Microalbuminuria Microvascular Dysfunction Neuropathy New Agents Non-Insulin-Dependent Diabetes Mellitus Outcome Participant Patients Persons Pharmaceutical Preparations Phenotype Population Positioning Attribute Pragmatic clinical trial Predictive Factor Prevalence Protocols documentation Public Health Quality of life Randomized Regimen Research Retinal Diseases Risk Risk Factors Secondary to Site Sulfonylurea Compounds Time Weight Gain Work basal insulin cardiovascular disorder risk comparative effectiveness cost effectiveness diabetes mellitus therapy economic cost effectiveness clinical trial follow-up glargine glucagon-like peptide 1 improved inhibitor/antagonist liraglutide premature prevent primary outcome recruit relative effectiveness response success

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项目摘要

Project Summary 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 ~28 million, incidence 1.4 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 ~5000 patients with recent-onset (<10 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 follow-up of approximately 4.8 (4-7.5) 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.

项目摘要影响世界人口的2型糖尿病（T2DM）的流行病威胁成为本世纪的主要公共卫生问题。巨大的人类和经济与美国流行病相关的成本（大约2800万，发病率为140万每年）与长期并发症的发展有关视网膜病变，肾病和神经病会导致更多的失明，肾衰竭和截肢比任何其他疾病。心血管疾病（CVD）增加了2-5倍 T2DM，是过早死亡的主要原因。高质量的临床试验已经建立降低血糖减少长期并发症的重要性。 T2DM的进展通常需要将第二代理添加到二甲双胍，即接受的第一行治疗。和开发了许多新类别的降糖药物，这是指导指导的证据缺乏第二代理的选择，促使相互冲突的准则的扩散确认这种缺陷。而且，尽管这些代理通常使用多年，但长期使用的数据不存在。比较有效性研究是高度优先改善公共卫生并最大化T2DM治疗的成本效益。此外，努力使T2DM疗法个性化并确定选定的疗法是否更好一些患者比其他患者需要的，以及了解的研究以了解随着时间的流逝，有关代谢的各种疗法。糖尿病的血糖减少方法：比较有效性（等级）研究将在约5000名患者的随机务实临床试验中解决这些问题近期发作（<10年）T2DM。等级将比较四个的代谢作用常见的降糖药物，磺酰尿素玻璃剂，DPP-4抑制剂西他列汀， GLP-1激动剂Liraglutide和碱性胰岛素glargine在临床上添加到二甲双胍中有意义的持续时间，平均随访约为4.8（4-7.5）年。主要结果是原发性代谢衰竭的时间（血红蛋白A1C（A1C）> 7％，随后确认）。其他结果包括平均A1C；时间到达次级代谢结果确认的A1C> 7.5％，然后将添加基本的胰岛素“救援”疗法；和不利诸如体重增加和低血糖症，对选定微血管疾病的影响以及 CVD风险因素，容忍度和生活质量以及成本和成本效益。我们也会检查与代谢相关的表型特征和病理生理因素对药物组合的反应和/或失败。