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

• 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
• 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

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(T2 DM)疫情威胁着 成为本世纪的主要公共卫生问题。巨大的人力和经济 与美国疫情相关的成本(流行率约为2800万，发病率为140万 每年)主要与长期并发症的发展有关，包括 视网膜病变、肾病和神经病变，导致更多的失明、肾功能衰竭和 截肢比其他任何疾病都要多。心血管疾病(CVD)增加了2-5倍 2型糖尿病是导致过早死亡的主要原因。已经建立了高质量的临床试验 降低血糖对减少长期并发症的重要性。2型糖尿病的进展 通常需要在二甲双胍的基础上添加第二种药物，这是公认的一线治疗方法。使用 众多新型降糖药物的开发，证据指导 缺乏第二种代理人的选择，促使相互矛盾的指导方针泛滥 承认这一缺陷。此外，虽然这些药剂通常使用多年， 关于长期使用的数据是不存在的。比较有效性研究是高度优先考虑的 改善公共健康，最大限度地提高治疗2型糖尿病的成本效益。此外, 努力使T2 DM治疗个体化，并确定选定的治疗方法是否在 需要一些患者而不是其他患者，以及了解不同药物的不同影响的研究 随着时间的推移，对新陈代谢的各种治疗方法。 糖尿病患者降血糖方法的有效性比较(分级) 这项研究将在约5000名患者中进行随机、务实的临床试验，以解决这些问题 最近发病(病程10年)的T2 DM。GRADE将比较四种药物对代谢的影响 常见的降糖药物，磺脲格列美脲，DPP-4抑制剂西格列汀， GLP-1激动剂利拉鲁肽和基础胰岛素甘精胰岛素，加入二甲双胍，临床上超过 有意义的持续时间，平均随访约4.8(4-7.5)年。初级阶段 结果是发生原发代谢衰竭的时间(血红蛋白A1C和GT；7%)，随后 其他结果包括平均A1C；达到次要代谢结果的时间 A1C&GT；7.5%，确诊后，将增加基础胰岛素“抢救”疗法；以及不良反应 体重增加和低血糖等影响，对选定的微血管疾病和 心血管疾病风险因素、耐受性和生活质量，以及成本和成本效益。我们还将 检测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。