Safety and Effectiveness Evaluations for Diabetes

糖尿病的安全性和有效性评估

• 批准号: 8225408
• 负责人: DONALD R MILLER
• 金额: --
• 依托单位: EDITH NOURSE ROGERS MEMORIAL VETERANS HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8225408
• 关键词: 2,4-thiazolidinedione; Acute Renal Failure with Renal Papillary Necrosis; Adverse event; Benefits and Risks; Cardiovascular Diseases; Cessation of life; Chronic Disease; Clinical; Clinical Trials; Congestive Heart Failure; Data; Diabetes Mellitus; Diabetic Angiopathies; Effectiveness; Epidemiologic Methods; Epidemiology; Evaluation; Event; Fracture; Future; Glimepiride; Glipizide; Glyburide; Heart failure; Hypoglycemia; Incidence; Kidney Diseases; Lactic Acidosis; Link; Metformin; Methodology; Myocardial Infarction; New Agents; Observational Study; Oral; Pancreatitis; Patients; Pharmaceutical Preparations; Pneumonia; Policies; Registries; Relative (related person); Relative Risks; Research; Resources; Risk; Safety; Sampling; Stroke; Sulfonylurea Compounds; Thiazolidinediones; Time; Uncertainty; cohort; comparative; cost; diabetes management; diabetes mellitus therapy; disability; exenatide; follow-up; glycemic control; health care service utilization; mortality

Diabetes mellitus is a burdensome, expensive, and increasingly common chronic illness that often leads to disability and death. Many new therapies for diabetes have emerged in recent years, but there continues to be concern and uncertainty regarding their safety and whether there are any incremental long term benefits. Information on these risks and benefits is unlikely to come from clinical trials in the foreseeable future and high quality observational studies of comparative safety and effectiveness are needed. We propose to study diabetes therapies using the Diabetes Epidemiology Cohorts (DEpiC), a national registry of all VA diabetes patients over more than a decade (about 2 million) that was established by our research team. Using up to 15 years of linked longitudinal national data, we will apply previously developed methodologies to compare medications for diabetes patients in terms of their safety and effectiveness. Drug-to-drug comparisons will be made among medications initially prescribed at different points in the course of diabetes treatment. For this proposal, we begin with a focus on the relative short-term and long-term safety of metformin, sulfonylurea, thiazolidinediones, and newer agents as well as a preliminary effectiveness analysis. Specifically we propose to evaluate relative risks of cardiovascular disease events (myocardial infarction, stroke, congestive heart failure) and mortality associated with use of metformin, sulfonylureas (glyburide, glipizide, glimepiride, older agents), and thiazolidinediones (rosigltizone, pioglitzone), by class and by specific drug within class. In addition, we will evaluate risks of various other adverse events associated with diabetes medications, including risk of lactic acidosis associated with metformin use, particularly in patients with early kidney disease or heart failure, risk of hypoglycemia associated with various sulfonylurea agents, risk of fracture associated with thiazolidinedione use, risks of pneumonia associated with sitagliptin use, and risks of pancreatitis and acute kidney injury associated with exenatide use. In addition we will conduct a preliminary analysis to evaluate diabetes medication effectiveness in terms of glycemic control, time to medication augmentation or switching, and effects on incidence and progression of microvascular complications. Health service utilization and costs will be estimated for observed effects of medication adverse events and benefits. For all evaluations, samples and exposure groups will be selected carefully to replicate common clinical decisions in treatment with application of rigorous epidemiologic methods to reduce potential bias and provide valid and meaningful results. One immediate benefit of this study is that it would provide new evidence related to current efforts in the VA to promote use of metformin as the oral agent of choice for most diabetes patients, including many previously considered to be contraindicated, with more limited use of sulfonyurea and newer agents. This research represents a real opportunity to better understand benefits and risks associated with treatments for diabetes and application of its findings should be used rapidly in adjusting policy for safer and more effective prescribing practices.

糖尿病是一种负担沉重、费用昂贵且日益常见的慢性疾病，通常会导致 残疾和死亡。近年来出现了许多新的糖尿病疗法，但 继续关注和不确定性，他们的安全，以及是否有任何增量 长期利益。关于这些风险和获益的信息不太可能来自临床试验， 安全性和有效性比较的可预见未来和高质量观察性研究， needed.我们建议使用糖尿病流行病学队列（DEpiC）研究糖尿病治疗， 超过十年（约200万）的所有VA糖尿病患者的国家登记处， 由我们的研究团队建立。使用长达15年的相关纵向国家数据，我们将 应用先前开发的方法，比较糖尿病患者的药物治疗， 其安全性和有效性。最初将在药物之间进行药物间比较 在糖尿病治疗过程中的不同时间点开药。 对于此提案，我们开始时， 关注二甲双胍、磺脲类、噻唑烷二酮类药物的相对短期和长期安全性， 新的代理商以及初步的有效性分析。具体而言，我们建议评估相对 心血管疾病事件（心肌梗死、卒中、充血性心力衰竭）的风险，以及 与使用二甲双胍、磺脲类药物（格列本脲、格列吡嗪、格列美脲、老年 药物）和噻唑烷二酮类（罗格列酮、吡格列酮）的数据。在 此外，我们将评估与糖尿病药物相关的各种其他不良事件的风险， 包括与二甲双胍使用相关的乳酸酸中毒风险，特别是在早期肾脏疾病患者中， 疾病或心力衰竭，与各种磺酰脲类药物相关的低血糖风险， 与噻唑烷二酮使用相关的骨折，与西格列汀使用相关的肺炎风险， 与exenetrant使用相关的胰腺炎和急性肾损伤风险。 此外，我们还将 初步分析，以评估糖尿病药物在血糖控制、至 药物增加或转换，以及对微血管病变发生率和进展的影响 并发症将根据观察到的药物效果估计卫生服务利用和费用 不良事件和获益。对于所有评价，将仔细选择样本和暴露组 应用严格的流行病学方法，重复常见的临床治疗决策 以减少潜在的偏差并提供有效和有意义的结果。这项研究的一个直接好处是 它将提供与VA当前努力相关的新证据，以促进二甲双胍作为 大多数糖尿病患者选择的口服药物，包括许多以前被认为是 禁忌，磺脲类和新型药物的使用更有限。这项研究代表了一个真实的 有机会更好地了解与糖尿病治疗相关的获益和风险， 应用其调查结果应迅速用于调整政策， 处方实践。