Effectiveness of Second Line Hypoglycemic Medications Among Veterans

退伍军人二线降血糖药物的有效性

• 批准号: 8330516
• 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 2016-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8330516
• 关键词: 18 year old; Acute myocardial infarction; Address; Adverse effects; Antidiabetic Drugs; Area; Blood Glucose; Blood Vessels; Cardiovascular Diseases; Cardiovascular system; Caring; Cause of Death; Cessation of life; Characteristics; Chronic Disease; Chronic Kidney Failure; Clinical; Clinical effectiveness; Cohort Studies; Combination Medication; Comorbidity; Complications of Diabetes Mellitus; Cox Proportional Hazards Models; Data; Data Set; Databases; Development; Diabetes Mellitus; Diabetic Angiopathies; Diagnosis; Disease; Distal; Drug usage; Effectiveness; Elements; Epidemiologic Studies; Exposure to; Failure; Glycosylated Hemoglobin; Glycosylated hemoglobin A; Goals; Guidelines; Health; Healthcare Systems; Heart Diseases; Hemoglobin; Hypoglycemia; Insulin; Interview; Judgment; Kidney; Kidney Diseases; Knowledge; Logistic Regressions; Measures; Mediating; Medical; Medicare; Metformin; Modeling; Observational Study; Oral; Outcome; Patients; Pattern; Persons; Pharmaceutical Preparations; Pharmacy facility; Pioglitazone; Population Heterogeneity; Probability; Provider; Recording of previous events; Regimen; Relapse; Research; Research Methodology; Research Proposals; Risk; Safety; Social support; Specific qualifier value; Stroke; Subgroup; Sulfonylurea Compounds; Time; Treatment Failure; Veterans; Vital Status; Weight; Weight Gain; Work; cardiovascular disorder risk; cardiovascular risk factor; cohort; common treatment; compliance behavior; diabetes mellitus therapy; diet and exercise; evidence base; experience; frailty; glycemic control; health administration; indexing; macrovascular disease; men who have sex with men; mortality; older patient; preference; randomized trial; rosiglitazone

DESCRIPTION (provided by applicant): Effectiveness of second line hypoglycemic medications among veterans Guidelines recommend metformin as the initial treatment for diabetes mellitus (DM) unless contraindicated, and also recommend a treatment target glycosylated hemoglobin (HbA1c) of <7%. Many patients require a second agent to reach these goals; however, little guidance is given for the selection of a second agent. Clinical judgement must be utilized and HbA1c goals of less than 7% may not be appropriate for some patients, particularly elderly patients and those with cardiovascular disease (CVD). While randomized trials often generate efficacy data, some trials do not include long-term outcomes; have a narrow spectrum of patients and may not compare relevant exposures to each other. Observational studies can help fill knowledge gaps and include diverse populations. This proposal will focus on real world decisions faced by clinicians and patients. We propose to answer key questions. Among patients using a single agent for the care of their diabetes and whose HbA1C is above goal on metformin monotherapy: What is the impact of insulin initiation compared to initiation of a second oral antidiabetic drug (OAD) on glycemic control, cardiovascular and renal outcomes? Among the subgroup of patients with pre-existing heart disease, what is the impact of no intensification versus intensification with any agent on the risk for cardiovascular and renal outcomes? This project will utilize national VHA data (Corporate Data Warehouse- Vital Signs File; pharmacy, SAS Medical datasets, VIReC Medicare data and VHA Vital status files) and National Death Index data to construct a national cohort of veterans with DM initially treated with metformin for a new diagnosis of DM (inception cohort). The proposed study follows this inception cohort to determine the patterns of drug use at the time they fail first line therapy (HbA1c >7.0% while on metformin). Given that metformin is recommended as first line therapy among many patients, we will study the addition of drugs to metformin to determine which regimen is most beneficial to risk intermediate outcomes such as HbA1C and long term outcomes such as CVD and renal outcomes. Persons included are aged >18 years, utilize the VA healthcare system between 10/30/2000 to 09/30/2010. The following exposures will be examined: 0= no DM drug, 1= metformin only, 2= metformin + insulin, 3= metformin + sulfonylurea 4= metformin+ pioglitazone 5=metformin+ rosiglitazone and 6= none of the above. Aim 1 will examine patient characteristics at the time of therapy initiation. Examined attributes will include administrative covariates plus those collected through chart review (Frailty index, diet, exercise, metformin adherence, and patient/provider information about treatment choice, and co-morbidities). We will use this information to help construct cohorts with similar covariates. Additionally, sensitivity analyses will quantify the size of a confounder that would explain our study findings. Aim 2 will examine glycemic effects of the second agent: the proportion who reach HbA1c of <7% and mean difference in HbA1c at 1 year as well as durability of glycemic control among those who have a second agent added and adverse effects including serious hypoglycemia. Aim 3 will examine the time to clinical outcomes including CVD (AMI, Stroke), chronic kidney disease (CKD) and all cause and cardiovascular mortality. We will use the marginal structural Cox proportional hazards models (MSM) using "stabilized" Inverse probability treatment weights (IPTW). The IPTW will be modeled using multinomial logistic regression incorporating fixed (baseline) and time-dependent exposures and covariates. The final stabilized weights used in the proposed MSMs will be calculated as the product of the treatment and censoring weights given each patient's static and time varying covariates over the previous time-points. Sensitivity analysis will be conducted to determine the effect of unmeasured confounders on risk of the outcome. The research team is poised to conduct a rigorous study on the safety and clinical effectiveness of second line therapies for DM.

描述（由申请人提供）： 退伍军人指南中二线降血糖药物的有效性建议二甲双胍作为糖尿病（DM）的初始治疗方法，除非是禁忌的，否则建议使用<7％的治疗靶糖基化血红蛋白（HBA1C）。许多患者需要第二个代理商才能实现这些目标；但是，几乎没有给出选择第二代理的指导。必须利用临床判断，HBA1C目标少于7％可能不适合某些患者，尤其是老年患者和患有心血管疾病的患者（CVD）。尽管随机试验通常会产生疗效数据，但一些试验不包括长期结果。具有狭窄的患者，可能不会将相关的暴露彼此比较。观察性研究可以帮助填补知识空白，并包括不同的人群。该建议将重点关注临床医生和患者面临的现实世界决策。我们建议回答关键问题。在使用单一药物来护理其糖尿病的患者中，其HBA1C对二甲双胍单一疗法的目标超过了：与第二种口服抗糖尿病药物（OAD）对血糖控制，心血管血管和肾脏成果的启动相比，胰岛素启动的影响是什么？在患有预先存在的心脏病的患者的亚组中，没有加强与任何药物对心血管和肾脏结局的风险有什么影响？该项目将利用国家VHA数据（公司数据仓库 - 生命体征文件；药房，SAS Medical数据集，VIREC Medicare数据和VHA生命状态文件）和国家死亡指数数据来构建由DM的全国退伍军人，最初用二甲甲甲型的DM处理DM（用于新的DM诊断）（Inception Colort）。拟议的研究遵循该成立队列，以确定药物使用模式在第一线治疗失败时（HbA1c> 7.0％，而在二甲双胍上）。鉴于在许多患者中建议将二甲双胍作为第一线治疗，我们将研究在二甲双胍中添加药物，以确定哪种方案对风险中间结果（例如HBA1C）和长期结局（例如CVD和肾脏结局）最有益。包括年龄> 18岁的人使用的人使用VA医疗保健系统在2000年10月30日至09/30/2010之间。将检查以下暴露：0 =无DM药物，1 =仅二甲双胍，2 =二甲双胍 +胰岛素，3 =二甲双胍 +磺基尿素4 =二甲双胍 +吡格列酮5 =二甲双胍 + sigiglitazone + rosiglitazone and 6 =以上没有。 AIM 1将在治疗开始时检查患者特征。所检查的属性将包括行政协变量以及通过图表审查收集的属性（较弱的指数，饮食，运动，二甲双胍的依从性以及有关治疗选择的患者/提供者的信息以及合并症）。我们将使用此信息来帮助与类似的协变量构建队列。此外，灵敏度分析将量化一种可以解释我们研究结果的混杂因素的大小。 AIM 2将检查第二种药物的血糖作用：在1年达到HBA1C <7％且平均差异的HBA1C的比例，以及在包括第二种药物和不良反应（包括严重低血糖症）的人中，血糖控制的耐用性。 AIM 3将检查包括CVD（AMI，中风），慢性肾脏疾病（CKD）以及所有原因和心血管死亡率在内的临床结果的时间。我们将使用“稳定”的逆概率处理权重（IPTW）使用边缘结构COX比例危害模型（MSM）。 IPTW将使用多项式逻辑回归进行建模，该回归结合了固定（基线）和时间依赖性的暴露和协变量。鉴于每个患者在以前的时间点上的静态和时间变化的协变量，将计算出建议的MSMS中使用的最终稳定权重作为治疗和检查权重的乘积。将进行灵敏度分析，以确定未衡量的混杂因素对结果风险的影响。研究小组准备对DM的第二线疗法的安全性和临床有效性进行严格的研究。