Effectiveness of Hypoglycemic Medications Among Veterans with CKD

患有 CKD 的退伍军人中降血糖药物的有效性

• 批准号: 10316978
• 负责人: Christianne L. Roumie
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-10-01 至 2024-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10316978
• 关键词: Accounting; Adult; Adverse effects; Agonist; Algorithms; American; Amputation; Ankle; Antidiabetic Drugs; Benefits and Risks; Cardiovascular Diseases; Cardiovascular system; Caring; Cessation of life; Clinical; Clinical Trials; Communities; Contracts; Cox Proportional Hazards Models; Data; Data Set; Diabetes Mellitus; Dipeptidyl Peptidases; Drug Costs; Drug Prescriptions; Echocardiography; Effectiveness; European; Evaluation; Event; Excretory function; Formularies; Fracture; GLP-2; GLP-I receptor; Glucose; Glycosylated hemoglobin A; Hearing; Heart failure; Hypoglycemia; Impairment; Investments; Kidney; Laboratories; Lipids; Longitudinal Studies; Marketing; Medical; Medicare/Medicaid; Methodology; Morbidity - disease rate; Myocardial Infarction; New Agents; Non-Insulin-Dependent Diabetes Mellitus; Observational Study; Outcome; Patients; Peripheral arterial disease; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacy facility; Phase; Physicians; Placebos; Policies; Probability; Publications; Regimen; Relative Risks; Reporting; Research; Risk; Safety; Side; Sodium; Stroke; Testing; Time; United States; United States Food and Drug Administration; Veterans; Veterans Health Administration; Vital Status; Weight; adverse event risk; aged; base; blood pressure intervention; bone; cardiovascular disorder risk; cardiovascular effects; cardiovascular risk factor; cohort; comparative effectiveness; cost; data warehouse; effectiveness evaluation; fracture risk; glycemic control; indexing; inhibitor; interest; liraglutide; men who have sex with men; mortality; novel therapeutics; pharmacy benefit; prevent; relative effectiveness; rosiglitazone; trial design

Approximately 30 million adults have diabetes (DM) in the United States and DM confers a risk for cardiovascular disease (CVD). Whether CVD is prevented by antidiabetic therapies which target glycemic control remains relatively unknown. Between 2013-2017 there were multiple pivotal trials of newer agent called sodium–glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP1RA) vs placebo. These newer agents demonstrated reduction in CVD and kidney outcomes. These new medications demonstrated lower risk of major adverse cardiovascular events (MACE) versus placebo with a pronounced effect among those with pre-existing CVD, and less data for those without CVD. But the trials also demonstrated increased risks of adverse events including a two-fold risk of amputations. There were both trial and post-marketing reports of fractures with SGLT2 because of impaired bone metabolite excretion. These medications are high cost; $300-$500 per month of treatment under VHA contracting. Use of these high cost medications if they prevented CVD would provide a return on investment. However, their efficacy is demonstrated vs placebo; their effectiveness relative to other commonly used medications remains unknown because data from real world cohorts is methodologically limited. Methodologically strong comparative effectiveness observational studies are necessary to determine the relative benefits We propose to conduct a National longitudinal study using administrative, clinical and laboratory data to quantify the relative risks/ benefits of DM agents among Veterans in two cohorts with and without CVD. This proposal will answer the question: Among patients with DM, what are the absolute risks of adverse events and potential cardiovascular and renal benefits for those who add on SGLT2 or GLP1RA compared to dipeptidyl peptidase 4 inhibitors (DPP4)? We will expand the cohort through FY2020 of Veterans with diabetes: utilizing national Veterans Health Administration (VHA) data (corporate data warehouse-vital signs; pharmacy, medical datasets, Medicare/ Medicaid data and vital status files), national death index and additional data on ankle brachial index and echocardiograms. Eligible veterans will be new users of SGLT2, GLP1RA or DPP4 aged >18 years who utilize VHA from 10/1/2000 through 09/30/2020. The current data (through FY 2016) has 35,799 SGLT2 new users; 68,876 new users of GLP1RA; and 203,030 new users of DPP4 (reference). We propose to evaluate the risks and benefits in 2 cohorts, those with and without CVD. The proposed study follows this cohort from new drug initiation until an outcome or censoring event (leave VHA, change therapy or death). The comparisons of interest will be: SGLT2 or GLP1RA vs. DPP4. Aim 1 will test the hypothesis that the risk of MACE (4 component- AMI/ Stroke/ CV death/ Heart failure) in patients treated with SGLT2 or GLP1RA is lower than the risk in patients treated with DPP4. Aim 2 will test the hypothesis that CKD progression and all-cause mortality is lower in patients treated with SGLT2 or GLP1RA vs. DPP4. Aim 3 will test the hypothesis that amputation and peripheral artery disease (PAD) revascularization is higher for patients treated with SGLT2 vs. DPP4. Aim 4 will test the hypothesis that risk of fracture is higher for patients treated with SGLT2 vs. DPP4. Propensity score weighting will be used to achieve similar groups. We will compare event rates accounting for baseline and time-varying covariates with marginal structural Cox proportional hazards models (MSM) with “stabilized” inverse probability treatment weights (IPTW). The execution of the proposed research will provide actionable evidence for patients with DM, would impact VHA policy and results would add to the oversight and costs of purchased community care for DM. Our team has been extremely productive over the last 7 years and is poised to conduct a rigorous and necessary evaluation of the effectiveness of newer DM regimens. Our publication record attests to our ability to use VHA data for accurate and impactful measurememnt of the safety and effectiveness of DM medications.

在美国，大约有3000万成年人患有糖尿病（DM），DM承认有风险 心血管疾病（CVD）。靶向血糖的抗糖尿病疗法是否可以阻止CVD 控制仍然相对未知。在2013-2017之间，有多次较新代理的关键试验称为 钠 - 葡萄糖共转运蛋白2（SGLT2）抑制剂和胰高血糖素样肽1受体激动剂（GLP1RA） vs安慰剂。这些较新的药物显示出CVD和肾脏结果的减少。这些新 药物表现出较低的主要不良心血管事件风险（MACE）与安慰剂相比 在患有CVD的患者中的明显效果，对于没有CVD的人来说，效果更少。但是试验也 证明不良事件的风险增加，包括截肢的两倍风险。都有两个试验 以及由于骨代谢物排泄受损而对SGLT2断裂的上市后报告。 这些药物是高成本； $ 300- $ 300- $ 500在VHA合同下的治疗。使用这些高 费用药物如果阻止CVD会提供投资回报。但是，他们的效率是 展示的与安慰剂；它们相对于其他常用药物的有效性仍然未知 因为从方法上，来自现实世界人群的数据受到限制。方法论上强的比较 有效性观察研究对于确定我们提出的相对益处是必要的 国家纵向研究使用行政，临床和实验室数据来量化相对风险/ 在有和没有CVD的两个队列中，退伍军人中DM代理的好处。 该建议将回答以下问题：在DM患者中，广告的绝对风险是什么 对于那些添加SGLT2或GLP1RA的人来说，事件以及潜在的心血管和肾脏益处 与二肽基胡椒4抑制剂（DPP4）相比？我们将通过2020财年扩展队列 糖尿病的退伍军人：利用国家退伍军人卫生管理局（VHA）数据（公司数据 仓库重要体征；药房，医疗数据集，医疗保险/医疗补助数据和生命状态文件），国家 死亡指数以及有关踝臂指数和超声心动图的其他数据。合格的退伍军人将是新的 SGLT2，GLP1RA或DPP4年龄> 18岁的用户从2000年10月1日至09/30/2020使用VHA。这 当前数据（通过2016财年）具有35,799个SGLT2新用户； 68,876名GLP1RA的新用户；和203,030 DPP4的新用户（参考）。我们建议评估两个人群中的风险和利益， 没有CVD。拟议的研究遵循从新药开始到结果或审查的该队列 事件（离开VHA，更改治疗或死亡）。感兴趣的比较将是：SGLT2或GLP1RA与。 DPP4。 AIM 1将检验以下假设：狼牙棒的风险（4个成分 - ami/ streose/ cv死亡/心力衰竭） 在接受SGLT2或GLP1RA治疗的患者中，患有DPP4治疗的患者的风险低。 AIM 2将测试 通过SGLT2或治疗的患者，CKD进展和全因死亡率较低的假说 GLP1RA与DPP4。 AIM 3将检验截肢和周围动脉疾病（PAD）的假设 SGLT2与DPP4治疗的患者的血运重建更高。 AIM 4将检验以下假设 SGLT2与DPP4治疗的患者骨折更高。倾向分数加权将用于实现 类似的组。我们将比较基线和时变协变量的事件率与边际 结构COX比例危害模型（MSM）具有“稳定”的反可能性处理权重 （IPTW）。拟议研究的执行将为DM患者提供可行的证据，将 影响VHA政策和结果将增加购买社区护理的监督和成本 DM。在过去的7年中，我们的团队一直非常有生产力，并被中毒以进行严格和 对新DM方案的有效性的必要评估。我们的出版记录证明了我们的能力 使用VHA数据来准确且有影响力的测量DM药物的安全性和有效性。