Safety and Effectiveness Evaluations for Diabetes

糖尿病是一种负担沉重、费用昂贵且日益常见的慢性疾病，它经常导致 致残致死。近年来出现了许多治疗糖尿病的新疗法，但 继续对它们的安全性以及是否有任何增量 长期利益。有关这些风险和益处的信息不太可能来自于 可预见的未来和高质量的相对安全性和有效性的观察性研究是 需要的。我们建议使用糖尿病流行病学队列来研究糖尿病的治疗方法。 十多年来(约200万人)所有退伍军人糖尿病患者的全国登记 由我们的研究团队建立。使用长达15年的纵向关联国家数据，我们将 应用以前开发的方法来比较糖尿病患者的药物治疗 它们的安全性和有效性。最初将在药物之间进行药物对药物的比较 在糖尿病治疗过程中的不同时间点开出的。对于这个提议，我们从一个 重点关注二甲双胍、磺脲、噻唑烷二酮类药物的相对短期和长期安全性 较新的药物以及初步的有效性分析。具体地说，我们建议评估相对 心血管疾病事件的风险(心肌梗塞、中风、充血性心力衰竭)和 与使用二甲双胍、磺脲类药物(格列本脲、格列吡嗪、格列美脲、老年人)相关的死亡率 药物)和噻唑烷二酮(罗格列酮、吡格列酮)，按类别和类别内的特定药物分类。在……里面 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， 包括与使用二甲双胍相关的乳酸酸中毒的风险，特别是在早期肾脏患者 疾病或心力衰竭，与各种磺脲类药物相关的低血糖风险， 与使用噻唑烷二酮相关的骨折，与使用西格列汀相关的肺炎风险，以及 与使用艾塞那肽相关的胰腺炎和急性肾损伤的风险。此外，我们还将进行 从血糖控制的角度评价糖尿病药物疗效的初步分析 药物强化或转换对微血管的发生和发展的影响 并发症。将根据观察到的用药效果估算卫生服务利用率和成本 不良事件和利益。对于所有评估，将仔细选择样本和暴露组 应用严格的流行病学方法在治疗中复制常见的临床决定 以减少潜在的偏见，并提供有效和有意义的结果。这项研究的一个直接好处是 它将提供与退伍军人管理局目前推广二甲双胍作为 大多数糖尿病患者的首选口服药物，包括许多以前被认为是 禁忌，磺脲类药物和较新药物的使用更加有限。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好处和风险 应迅速利用其调查结果调整政策，以实现更安全和更有效的政策 开药方的做法。

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.