Safety and Effectiveness Evaluations for Diabetes

糖尿病是一种负担重、昂贵且日益常见的慢性疾病，通常会导致 致残疾和死亡。近年来出现了许多治疗糖尿病的新疗法，但 仍然对他们的安全以及是否有任何增量感到担忧和不确定 长期利益。有关这些风险和益处的信息不太可能来自临床试验 可预见的未来和比较安全性和有效性的高质量观察研究 需要。我们建议使用糖尿病流行病学队列 (DEpiC) 研究糖尿病治疗方法，该队列是 十多年来所有 VA 糖尿病患者（约 200 万）的国家登记 由我们的研究团队建立。使用长达 15 年的关联纵向国家数据，我们将 应用先前开发的方法来比较糖尿病患者的药物治疗 他们的安全性和有效性。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阶段服用。 对于这个提案，我们首先 重点关注二甲双胍、磺酰脲类、噻唑烷二酮类药物的相对短期和长期安全性 新药剂以及初步效果分析。具体来说，我们建议评估相对 心血管疾病事件（心肌梗塞、中风、充血性心力衰竭）的风险和 与使用二甲双胍、磺酰脲类药物（格列本脲、格列吡嗪、格列美脲、老年药物）相关的死亡率 剂）和噻唑烷二酮类（罗格列酮、吡格列酮），按类别和类别内的特定药物。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， 包括与使用二甲双胍相关的乳酸性酸中毒的风险，尤其是早期肾病患者 疾病或心力衰竭、与各种磺酰脲类药物相关的低血糖风险、 与使用噻唑烷二酮相关的骨折、与使用西他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 初步分析评估糖尿病药物在血糖控制、治疗时间方面的有效性 药物增加或转换，以及对微血管的发生和进展的影响 并发症。将根据观察到的药物效果来估计卫生服务的利用率和成本 不良事件和益处。对于所有评估，样品和暴露组都将经过仔细选择 应用严格的流行病学方法来复制常见的临床治疗决策 减少潜在的偏见并提供有效且有意义的结果。这项研究的一个直接好处是 它将提供与退伍军人事务部目前为促进二甲双胍的使用而做出的努力相关的新证据 大多数糖尿病患者（包括许多以前被认为是糖尿病患者）选择的口服药物 禁忌症，磺脲类药物和较新药物的使用受到更多限制。这项研究代表了真实的 有机会更好地了解与糖尿病治疗相关的益处和风险 其研究结果的应用应迅速用于调整政策，以实现更安全、更有效的目标 规定做法。

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.