Comparative Effectiveness and Safety of Newer and Older Antihyperglycemic Medications

新旧抗高血糖药物的有效性和安全性比较

基本信息

批准号：
10730533
负责人：
Ziyad Al-Aly
金额：
--
依托单位：
ST. LOUIS VA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-01 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10730533
关键词：
Accounting Acute Renal Failure with Renal Papillary Necrosis Address Adverse event Affect Age Agonist Albumins Albuminuria Algorithms Benefits and Risks Big Data Bladder Body mass index Cardiovascular Agents Cardiovascular Diseases Cardiovascular system Caring Categories Cessation of life Characteristics Chronic Kidney Failure Clinical Practice Guideline Complex Computerized Medical Record Creatinine Data Diabetes Mellitus Diabetic Ketoacidosis Diagnosis Dipeptidyl Peptidases Disease Outcome Disease Progression Effectiveness Electronic Health Record Eligibility Determination End stage renal failure Event Fracture Future GLP-I receptor Glomerular Filtration Rate Glucose Health Services Research Healthcare Heart Diseases Heart failure Hospitalization Hypertension Hypoglycemia Hypoglycemic Agents Incidence Individual Informatics Intention Kidney Kidney Diseases Knowledge Life Style Lower Extremity Machine Learning Metformin Methodology Methods Myocardial Infarction New Agents Outcome Outcome Assessment Patients Persons Pharmaceutical Preparations Pharmacoepidemiology Placebos Population Probability Protocols documentation Race Randomized Randomized, Controlled Trials Reducing Agents Renal function Reporting Research Priority Resources Risk Risk Assessment Risk Estimate Risk Reduction Safety Sodium Specific qualifier value Stroke Subgroup Sulfonylurea Compounds Survival Analysis Time United States Department of Veterans Affairs Urinary tract infection Urine Veterans Work acute pancreatitis adverse event risk arm cardiovascular disorder risk cardiovascular risk factor clinical practice cohort comparative comparative effectiveness comparative effectiveness trial comparative safety cost diabetes mellitus therapy diabetes risk discrete time falls follow-up hazard heart disease risk high dimensionality high risk high risk population inhibitor innovation kidney preservation limb amputation mortality novel therapeutics personalized care primary care practice randomized trial randomized, clinical trials research and development symporter treatment guidelines treatment strategy venous thromboembolism

Accounting Acute Renal Failure with Renal Papillary Necrosis Address Adverse event Affect Age Agonist Albumins Albuminuria Algorithms Benefits and Risks Big Data Bladder Body mass index Cardiovascular Agents Cardiovascular Diseases Cardiovascular system Caring Categories Cessation of life Characteristics Chronic Kidney Failure Clinical Practice Guideline Complex Computerized Medical Record Creatinine Data Diabetes Mellitus Diabetic Ketoacidosis Diagnosis Dipeptidyl Peptidases Disease Outcome Disease Progression Effectiveness Electronic Health Record Eligibility Determination End stage renal failure Event Fracture Future GLP-I receptor Glomerular Filtration Rate Glucose Health Services Research Healthcare Heart Diseases Heart failure Hospitalization Hypertension Hypoglycemia Hypoglycemic Agents Incidence Individual Informatics Intention Kidney Kidney Diseases Knowledge Life Style Lower Extremity Machine Learning Metformin Methodology Methods Myocardial Infarction New Agents Outcome Outcome Assessment Patients Persons Pharmaceutical Preparations Pharmacoepidemiology Placebos Population Probability Protocols documentation Race Randomized Randomized, Controlled Trials Reducing Agents Renal function Reporting Research Priority Resources Risk Risk Assessment Risk Estimate Risk Reduction Safety Sodium Specific qualifier value Stroke Subgroup Sulfonylurea Compounds Survival Analysis Time United States Department of Veterans Affairs Urinary tract infection Urine Veterans Work acute pancreatitis adverse event risk arm cardiovascular disorder risk cardiovascular risk factor clinical practice cohort comparative comparative effectiveness comparative effectiveness trial comparative safety cost diabetes mellitus therapy diabetes risk discrete time falls follow-up hazard heart disease risk high dimensionality high risk high risk population inhibitor innovation kidney preservation limb amputation mortality novel therapeutics personalized care primary care practice randomized trial randomized, clinical trials research and development symporter treatment guidelines treatment strategy venous thromboembolism

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项目摘要

Background: People diagnosed with diabetes are initially advised on lifestyle changes and started on metformin, but often require the addition of 2nd line antihyperglycemic medications. The choice of 2nd line antihyperglycemic therapy is complex because the multiple available drugs, distributed across several drug classes, have different benefits and risks. Newer 2nd line antihyperglycemics (sodium-glucose co-transporter-2 inhibitor (SGLT2i), and glucagon-like peptide-1 receptor agonist (GLP1)) have been shown to reduce risk of cardiovascular events compared to placebo in individuals at high risk of cardiovascular disease. Evidence also suggests that these newer agents may reduce risk of kidney disease in people with relatively preserved kidney function. Whether the newer agents offer benefits in cardiovascular and kidney outcomes compared to older (less costly) 2nd line agents including dipeptidyl peptidase-4 inhibitors (DPP4) and sulfonylureas, and whether these benefits extend to individuals with intermediate or low cardiovascular risk and people with reduced kidney function is not known. Significance/Impact: Results will provide real-world evidence to guide the selection of antihyperglycemic agents by cardiovascular risk status, kidney function category, and will provide evidence on the risk of adverse events. The proposal falls under several Health Services Research priorities including Primary Care Practice (diabetes is highly prevalent in veterans) and Health Care Informatics (using big data to advance care of veterans); and Office of Research & Development priorities as our approach will highlight VA data as a national resource and the results will have direct and substantial real-world impact in informing care. Innovation: The proposal will leverage the power of the VA’s large-scale electronic health records and recent methodologic innovations in causal inference and pharmacoepidemiology — specifically in the use of real- world observational data to emulate a target randomized trial — to provide much needed evidence of the comparative effectiveness and safety of newer vs. older antihyperglycemic agents. Specific Aims: To use observational healthcare data from the Department of Veterans Affairs to emulate four- arm randomized trials of the comparative effectiveness of incident use of newer (SGLT2i, GLP1) and older (DPP4, sulfonylureas) 2nd line antihyperglycemics—among metformin users—on cardiovascular outcomes (aim 1), kidney outcomes (aim 2), and evaluate the risk of adverse events associated with these drug classes (aim 3). Methodologies: For each specific aim we will define a target randomized trial protocol, including eligibility criteria, treatment assignment, treatment initiation, treatment strategy follow-up, outcome assessment, and analytic plan. We then will use electronic medical record data from the VA to construct aim-specific cohorts to emulate the specifications of the target trial for the related aim, estimating the differences in risk of cardiovascular disease, kidney disease, and adverse events between the studied antihyperglycemics. Randomization will be emulated by inverse probability of treatment weighting based on predefined variables and a high dimensional variable selection algorithm. Intention-to-treat effects will be estimated using discrete time survival analyses, and adjusted intention-to-treat-effects will be estimated after accounting for loss to follow-up. Per-protocol effects (of a specified treatment strategy) will be estimated after accounting for non- adherence to assigned treatment strategies. Differences in risk of outcomes between the second-line antihyperglycemics will be reported as hazard ratios and adjusted incidence rates. Implementation/Next Steps: The results from this proposal will inform clinical practice guidelines for the treatment of diabetes. Future studies will leverage advances in machine learning to create unique individualized precision care plans for each person with diabetes.

背景：最初建议被诊断出患有糖尿病的人的生活方式改变并开始二甲双胍，但通常需要添加第二线抗血糖药物。第二行的选择抗血糖疗法很复杂，因为多种可用药物分布在几种药物中课程，有不同的好处和风险。较新的第二线抗蛋白质（钠 - 葡萄糖共转运蛋白2）抑制剂（SGLT2I）和胰高血糖素样肽-1受体激动剂（GLP1）已显示可降低与安慰剂相比，心血管疾病的高风险中的心血管事件。也证据表明这些较新的药物可能会降低相对保存的肾脏患者的肾脏疾病风险功能。与年龄较大的人相比（成本较低）的第二线药物，包括二肽基肽-4抑制剂（DPP4）和磺酰尿菌，以及是否是否这些好处扩展到患有中级或低心血管风险的人，并且有降低的人肾功能尚不清楚。意义/影响：结果将提供现实世界的证据，以指导抗血糖的选择通过心血管风险状态，肾功能类别的代理商，将提供有关广告风险的证据事件。该提案属于包括初级保健在内的几个卫生服务研究重点实践（糖尿病在退伍军人中非常普遍）和医疗保健信息学（使用大数据来推进照顾退伍军人）；和研究与发展优先办公室作为我们的方法将重点介绍VA数据作为国家资源，结果将在为护理提供信息方面具有直接和重大的现实影响。创新：该提案将利用VA的大规模电子健康记录和最新的功能因果推理和药物ePidemiology的方法论创新 - 特别是使用世界观察数据模仿目标随机试验 - 提供急需的证据与较老的抗血糖药物的比较有效性和安全性。具体目的：使用退伍军人事务部的观察医疗保健数据模仿四个武器随机试验新较新的（SGLT2I，GLP1）和较老的事件使用的比较有效性（DPP4，磺酰尿）第二行抗蛋白质 - 二甲双胍用户 - 心血管结果（AIM 1），肾脏结局（AIM 2），并评估与之相关的不良事件的风险毒品类（目标3）。方法论：对于每个特定目标，我们将定义目标随机试验方案，包括资格标准，治疗分配，治疗计划，治疗策略随访，结果评估和分析计划。然后，我们将使用来自VA的电子病历数据来构建特定于AIM的队列模仿相关目标的目标试验的规格，估计在研究分解的抗血糖之间的心血管疾病，肾脏疾病和不良事件。基于预定义变量的治疗加权的逆概率将模拟随机分组以及高维变量选择算法。意图对治疗效果将使用离散估算时间生存分析和调整后的意向性治疗效果将在考虑到损失后估计后续。（指定治疗策略）将估算出非 - 遵守指定的治疗策略。二线结局风险差异抗血糖的危险比和调整后的事件率将报道。实施/下一步：该提案的结果将为临床实践指南提供信息糖尿病的治疗。未来的研究将利用机器学习的进步来创造独特的每个糖尿病患者的个性化精度护理计划。