Effectiveness of Immediate vs. Delayed Use of Metformin in New-Onset T2 Diabetes

立即使用二甲双胍与延迟使用二甲双胍治疗新发 T2 糖尿病的疗效

• 批准号: 7820749
• 负责人: JOE Vandiver SELBY
• 金额: $ 48.17万
• 依托单位: KAISER FOUNDATION RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-25 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7820749
• 关键词: Acute; Acute myocardial infarction; Address; Adopted; Adoption; Age; American; American Heart Association; Antihypertensive Agents; Area; Blood Glucose; Body mass index; Cardiology; Cardiovascular Diseases; Clinical; Clinical Trials; Complement; Complications of Diabetes Mellitus; Computerized Medical Record; Congestive Heart Failure; Consensus; Coronary; Data; Detection; Deterioration; Diabetes Mellitus; Diabetes prevention; Diabetic Angiopathies; Diabetic Retinopathy; Diagnosis; Diagnostic; Early Diagnosis; Early treatment; Effectiveness; Ethnic Origin; Event; Failure; Gender; Glomerular Filtration Rate; Glyburide; Guidelines; Health system; Healthcare Systems; Heart Diseases; High Density Lipoprotein Cholesterol; Hypoglycemia; Incidence; Kidney Diseases; LDL Cholesterol Lipoproteins; Life Style; Lipids; Low-Density Lipoproteins; Measures; Medical Nutrition Therapy; Metformin; Microalbuminuria; Natural History; Natural experiment; Newly Diagnosed; Non-Insulin-Dependent Diabetes Mellitus; Observational Study; Oral; Outcome; Pancreas; Patients; Peripheral; Pharmaceutical Preparations; Pharmacotherapy; Physicians; Population; Prevalence; Race; Recommendation; Records; Registries; Relative (related person); Research; Risk; Scoring Method; Stroke; Sulfonylurea Compounds; System; Time; Treatment Protocols; Variant; Weight Gain; base; blood pressure regulation; cardiovascular disorder risk; cardiovascular risk factor; cholesterol control; clinical practice; cohort; college; comparative effectiveness; diabetes prevention program; diabetic patient; evidence base; follow-up; glycemic control; impaired glucose tolerance; improved; insulin secretion; macrovascular disease; member; patient population; prevent; response

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (05) Comparative Effectiveness and Specific Challenge Topic 05-DK-101* Selecting the Optimal Initial Treatment Regimen for Patients With Newly Discovered Type 2 Diabetes. Recommendations for initial pharmacotherapy in type 2 diabetes were modified in 2007 - to change from sulfonylureas to metformin as initial monotherapy, and from recommending an initial trial of medical nutrition therapy (MNT) and lifestyle change to recommending prompt initiation of pharmacotherapy along with MNT at initial diagnosis of diabetes. Findings from UKPDS and from two observational studies suggest that metformin monotherapy may lower risk for cardiovascular complications relative to sulfonylureas; findings from the ADOPT Study indicate that durability of monotherapy effectiveness is longer with metformin than with the sulfonylurea glyburide. Metformin also appears to have a modest relative benefit on LDL- cholesterol levels and usually does not cause hypoglycemia. Evidence from the Diabetes Prevention Program demonstrates that metformin is effective in preventing progression from impaired glucose tolerance to diabetes, suggesting that it may also be effective in slowing deterioration of pancreatic function once the diagnostic threshold for type 2 diabetes has been crossed if started immediately. Recent recommendations in response to the ACORD, ADVANCE, and VADT trials also suggest that early glycemic control may be more effective than later in preventing both microvascular and macrovascular complications of type 2 diabetes. These guidelines are acknowledged by their authors to be "consensus-based" and the need for better evidence, especially with respect to longer-term outcomes is clearly stated. They have not been widely adopted in clinical practice, and it is unknown whether they are impacting outcomes in diverse, real-world, patient populations. Undoubtedly, there has been variation in adoption across physicians, systems, and time, providing this "natural experiment" opportunity to study whether early initiation of metformin is superior to prior practice for delaying deterioration of diabetes and the onset of complications. We propose to examine the comparative effectiveness of immediate initiation of metformin monotherapy vs. delayed initiation of metformin or early/late initiation of sulfonylurea monotherapy for a variety of outcomes. Using electronic medical record data from 4 large health system members of the HMO Research Network Diabetes Consortium, we will create a large cohort of newly diagnosed type 2 diabetic patients with average follow-up of 3.5 years. In longitudinal analyses, we will examine whether prompt initiation of metformin (within 6 months of the earliest detection of diabetes) compared with other strategies is associated with: 1. Longer durability of glycemic control on monotherapy (from initial detection of diabetes to failure of monotherapy) 2. Less weight gain at 1 and 2 years post initial diagnosis 3. Differences in the incidence of severe hypoglycemia 4. Better LDL-cholesterol control or lower intensity of lipid-lowering therapy required 5. Differences in blood pressure control or lower intensity of anti-hypertensive therapy required 6. Differences in the incidence of cardiovascular disease endpoints (combined endpoint of acute myocardial infarction, stroke, or coronary, carotid or peripheral revascularization) 7. Differences in incidence of microvascular complications (new onset diabetic retinopathy, microalbuminuria, or rate of decline in estimated glomerular filtration rate). We recognize the risks of confounding inherent in observational approaches. Many clinical and demographic confounders are available to us from EMR records and all comparisons will be adjusted, using propensity scores, for these variables measured at or before initial detection of diabetes. As a complement to these analyses, we will conduct instrumental variable analyses, using physician prescribing practices as the instrumental variable. Recent studies suggest that metformin is the best oral medication for initial treatment of diabetes and that starting metformin immediately when diabetes is first detected, rather than waiting until blood sugars reach a somewhat higher target level, could delay progression of diabetes and prevent complications such as heart disease, stroke and kidney disease. This study compares very early treatment with metformin to more traditional approaches in a population of nearly 40,000 newly diagnosed diabetic patients from 4 large health care systems. If an advantage is shown for early use of metformin, the study's findings could dramatically change the way in which type 2 diabetes is treated in the U.S. and reduce the burden of complications from this very common condition.

描述（由申请人提供）：此申请解决广泛的挑战区域（05）比较有效性和特定挑战主题05-DK-101*选择新发现的2型糖尿病患者的最佳初始治疗方案。 2007年对2型糖尿病的初始药物疗法的建议进行了改造 - 从磺酰氟菌转变为二甲双胍作为初步单一疗法，并建议对医疗营养疗法（MNT）的初步试验和生活方式改变，并建议迅速启动药物治疗以及MNT在初步诊断糖尿病时进行药物治疗。 UKPD和两项观察性研究的发现表明，二甲双胍单一疗法可能会降低相对于磺酰氟烷的心血管并发症的风险。收养研究的发现表明，单药治疗效果的耐用性与二甲双胍的耐用性要比磺胺尿素格列班更长。二甲双胍似乎也对LDL-胆固醇水平具有适中的相对益处，通常不会引起低血糖症。糖尿病预防计划的证据表明，二甲双胍可有效预防糖尿病葡萄糖耐受性受损受损的进展，这表明一旦立即启动了2型2型糖尿病的诊断阈值，它也可以有效减慢胰腺功能的恶化。最近对ACORD，Advance和VADT试验的建议还表明，早期血糖控制可能比以后预防2型糖尿病的微血管和大血管并发症更有效。他们的作者认为这些准则是“基于共识的”，并且需要更好的证据，尤其是在长期结局方面。它们在临床实践中尚未被广泛采用，尚不清楚它们是否影响了多样化的现实世界，患者人群的结果。毫无疑问，在医师，系统和时间之间的采用方面存在差异，提供了这种“自然实验”的机会，以研究二甲双胍早期开始是否优于先前的实践来延迟糖尿病恶化和并发症的发作。我们建议检查二甲双胍单药治疗与二甲双胍的延迟开始或磺酰脲单一疗法的早期/晚期开始的比较有效性。使用来自HMO研究网络糖尿病财团的4个大型卫生系统成员的电子病历数据，我们将创建大量新诊断的2型糖尿病患者，平均随访为3。5年。在纵向分析中，我们将检查与其他策略相比，与其他策略相比，是否迅速启动二甲双胍（在最早发现糖尿病的6个月内）是否与：1。血糖控制对单层疗法的较长耐用性更长的耐用性（从最初检测到糖尿病的最初检测到单疗法失败到单疗法的失败到最初的诊断后1和2年的重量较小。控制脂质疗法的控制强度或较低的强度需要5。血压控制或降低抗高血压疗法的差异需要6。心血管疾病终点的发病率差异（急性心肌梗死，中风，中风，冠状动脉或冠状动脉或外周或外围或外围的临床差异）7。视网膜病变，微量白蛋白尿或估计肾小球滤过率下降率）。我们认识到观察方法中固有的混淆的风险。我们可以从EMR记录中获得许多临床和人口统计混杂因素，并且将使用倾向分数调整所有比较，以在初始检测到糖尿病时测量的这些变量。作为对这些分析的补充，我们将使用处方实践作为仪器变量进行仪器变量分析。最近的研究表明，二甲双胍是最初治疗糖尿病的最佳口服药物，并且在首次检测到糖尿病时立即开始二甲双胍，而不是等到血糖达到较高的靶标水平，可能会延迟糖尿病的进展并防止并发症，例如心脏病，中风和肾脏病。这项研究将二甲双胍的早期治疗与来自4个大型医疗保健系统的近40,000名新诊断的糖尿病患者的人群中的更传统方法进行了比较。如果显示出可及早使用二甲双胍的优势，则该研究的发现可能会大大改变美国治疗2型糖尿病的方式，并减轻这种非常常见的状况的并发症负担。