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

• 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
• 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

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）：影响世界人口的2型糖尿病（T2DM）的流行有可能成为本世纪的主要公共卫生问题。与美国流行病相关的巨大人类和经济成本（约2500万，每年发病率为190万）主要与长期并发症的发展有关，包括视网膜病变，肾病和神经病，导致更多的盲目性，肾衰竭，肾衰竭，肾脏失败和截肢病例更多。心血管疾病（CVD）在T2DM中增加了2-5倍，是过早死亡的主要原因。高质量的临床试验已经确定了降低血糖以减少长期并发症的重要性。 T2DM的进展通常需要将第二个药物添加到二甲双胍，即接受的第一线治疗。随着众多新类别降糖药物的开发，缺乏指导第二代理的指导选择的证据，这促使人们承认这种不足的指南的扩散。此外，尽管这些代理通常使用多年，但长期使用的数据是不存在的。比较有效性研究是改善公共卫生和最大化T2DM治疗成本效益的高度优先事项。此外，为某些患者的个性化T2DM疗法并确定某些患者的努力是否比其他患者的效果更好，并且研究以了解各种疗法随着时间的推移对代谢的差异影响。 糖尿病中的血糖减少方法：一项比较有效性（等级）研究将在6000例近期发病（<5年）T2DM的随机务实临床试验中解决这些问题。等级将比较四种常见的降糖药物的代谢作用，磺酰尿素Glimepiride，DPP-4抑制剂西塔列汀，GLP-1激动剂liraglutide和基底胰岛素粘蛋白，在临床上有意义的持续时间为4.5（3-6-6-6）。主要结果是原发性代谢衰竭的时间（血红蛋白A1C（A1C）> 7％，随后得到确认）。其他结果包括平均A1C；确认，将A1C> 7.5％的次级代谢结果> 7.5％的时间进行确认，此后将添加基础胰岛素“救援”疗法；体重增加和低血糖症，对选定的微血管疾病和CVD风险因素的影响，耐受性和生活质量以及成本和成本效益等不利影响。我们还将检查与药物组合的代谢反应和/或失败有关的表型特征和病理生理因素。