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: 9117509
• 负责人: JOHN M LACHIN
• 金额: $ 2998.06万
• 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/9117509
• 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; 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; Microvascular Dysfunction; Neuropathy; New Agents; Non-Insulin-Dependent Diabetes Mellitus; Outcome; Participant; Patients; Persons; Pharmaceutical Preparations; Population; Positioning Attribute; Pragmatic clinical trial; Prevalence; 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; 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(申请人提供)：影响世界人口的2型糖尿病(T2 DM)流行有可能成为本世纪的主要公共卫生问题。在美国，与疫情相关的巨大人力和经济代价(患病率约为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、肾病和神经病变，这些并发症导致的失明、肾功能衰竭和截肢病例比其他任何疾病都多。心血管疾病(CVD)在T2 DM患者中增加2-5倍，是导致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。T2 DM的进展通常需要在二甲双胍的基础上增加第二种药物，这是公认的一线治疗方法。随着大量新的降糖药物的开发，缺乏指导第二种药物选择的证据，促使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，但关于长期使用的数据并不存在。比较有效性研究是改善公众健康和最大限度提高2型糖尿病治疗成本效益的高度优先事项。此外，需要努力使T2 DM治疗个体化，并确定选定的治疗方法在某些患者中是否比其他患者效果更好，以及了解不同治疗方法随时间对新陈代谢的不同影响的研究。降低糖尿病血糖的方法：一项比较有效性(等级)研究将在6000名新近发病的(5年)T2 DM患者中进行随机、务实的临床试验，以解决这些问题。GRADE将比较四种常见降糖药物，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，在临床上有意义的持续时间内，平均暴露4.5(3-6年)年。主要结果是达到初级代谢衰竭的时间(血红蛋白A1C和GT；7%，后来得到确认)。其他结果包括平均A1C；达到次级代谢结果的时间A1C和GT；7.5%，确认后，将添加基础胰岛素“拯救”治疗；以及不良反应，如体重增加和低血糖，对选定的微血管疾病和心血管危险因素的影响，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。