CV Benefits and Safety of Glucose-Lowering Therapies in Adults with Diabetes

成人糖尿病患者降糖疗法的心血管益处和安全性

基本信息

批准号：
9292370
负责人：
PATRICK J O'CONNOR
金额：
$ 73.92万
依托单位：
HEALTHPARTNERS INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-01 至 2020-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9292370
关键词：
Address Adult Affect Agonist American Benefits and Risks Blood Pressure Cardiovascular system Caring Cause of Death Cholesterol Clinical Clinical Data Comorbidity Complement Congestive Heart Failure Diabetes Mellitus Event Excess Mortality Exclusion GLP-I receptor Glucose Glycosylated hemoglobin A Goals Hospitalization Human Insulin Intervention LDL Cholesterol Lipoproteins Metformin Minority Modernization Myocardial Infarction Non-Insulin-Dependent Diabetes Mellitus Outcome Pathway interactions Patients Persons Pharmaceutical Preparations Pharmacological Treatment Population Probability Provider Public Health Regimen Safety Sampling Selection Bias Stroke Structural Models Subgroup Sulfonylurea Compounds Testing Thiazolidinediones Time Weight age group analog analytical method basal insulin base blood glucose regulation cardiovascular risk factor clinical care community setting comparative effectiveness design follow-up glucagon-like peptide 1 improved indexing inhibitor/antagonist mortality novel public health relevance treatment duration

项目摘要

DESCRIPTION (provided by applicant): Cardiovascular (CV) events are the most common cause of death in adults with type 2 diabetes. While the benefits and safety of commonly used blood pressure (BP) and cholesterol medications are well established, much less is known about the CV benefits and CV risks of commonly used glucose-control strategies involving treatment with multiple glucose-lowering agents. To address this important clinical and public health concern, this project examines detailed clinical data from 1.3 million adults with treated type 2 diabetes over a 13-year period to quantify the impact of specific combinations of glucose-lowering agents on myocardial infarction, stroke, CV mortality, total mortality, and congestive heart failure (CHF) hospitalizations. We test four comparative effectiveness hypotheses to determine whether major CV events are differentially related to: (a) use of specific two-agent combinations of metformin with sulfonylurea (SU), thiazolidinedione (TZD), DPP-4 inhibitors, or GLP-1 receptor agonists; (b) use of specific two-agent combinations of metformin with SU, TZD, DPP-4 inhibitors, or GLP-1 receptors agonists when basal insulin is added; (c) addition of prandial insulin in subjects already using basal insulin; and (d) treatment with human insulin versus analog insulin. Analysis employs modern comparative effectiveness statistical approaches, including new user designs and marginal structural modeling (MSM) with inverse probability weighting (IPW) and targeted minimal loss-based estimation (TMLE) which, under certain conditions, allow proper adjustment for time-dependent confounders on the causal pathway between early exposures and clinical outcomes, as well as proper adjustment for selection bias due to informative censoring. The study results have the potential to substantially improve CV outcomes in millions of Americans with type 2 diabetes by identifying which commonly used glucose-lowering regimens maximize CV benefits and minimize CV risks.

描述（由申请人提供）：心血管 (CV) 事件是成人 2 型糖尿病患者最常见的死亡原因。虽然常用的降压 (BP) 和降胆固醇药物的益处和安全性已得到充分证实，但人们对涉及多种降糖药物治疗的常用血糖控制策略的 CV 益处和 CV 风险知之甚少。为了解决这一重要的临床和公共卫生问题，该项目检查了 130 万名患有 2 型糖尿病的成人在 13 年期间接受治疗的详细临床数据，以量化特定降糖药物组合对心肌梗塞、中风、心血管疾病的影响死亡率、总死亡率和充血性心力衰竭 (CHF) 住院治疗。我们测试了四种比较有效性假设，以确定主要 CV 事件是否与以下因素存在差异相关：(a) 使用二甲双胍与磺酰脲 (SU)、噻唑烷二酮 (TZD)、DPP-4 抑制剂或 GLP-1 受体的特定双药组合激动剂； (b) 当添加基础胰岛素时，使用二甲双胍与 SU、TZD、DPP-4 抑制剂或 GLP-1 受体激动剂的特定双药组合； (c) 在已经使用基础胰岛素的受试者中添加餐时胰岛素； (d)用人胰岛素治疗与胰岛素类似物治疗。分析采用现代比较有效性统计方法，包括新的用户设计和具有逆概率加权（IPW）的边际结构建模（MSM）和有针对性的最小基于损失的估计（TMLE），在某些条件下，允许对时间相关的混杂因素进行适当的调整关于早期暴露和临床结果之间的因果关系，以及对由于信息审查而导致的选择偏差的适当调整。该研究结果有可能通过确定哪些常用的降糖疗法可以最大限度地提高心血管益处并最大限度地降低心血管风险，从而显着改善数百万患有 2 型糖尿病的美国人的心血管结局。