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

• 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
• 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

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2型糖尿病成人中最常见的死亡原因。尽管已经确定了常用血压（BP）和胆固醇药物的益处和安全性，但对CV的益处和简历风险的了解却少得多，而常用使用的葡萄糖控制策略涉及多种降糖剂的治疗。为了解决这一重要的临床和公共卫生问题，该项目在13年期间检查了130万接受治疗2型糖尿病的成年人的详细临床数据，以量化降低葡萄糖的特定组合对心肌梗塞，中风，CV死亡率，总死亡率，总死亡率和充血性心力衰竭（CHF）住院的影响。我们测试了四个比较有效性假设，以确定主要的CV事件是否与：（a）使用二甲双胍与磺酰尿素（SU），硫代唑烷二酮（TZD），DPP-4抑制剂或GLP-1受体受体的特定两种代理组合； （b）当添加基础胰岛素时，将二甲双胍与SU，TZD，DPP-4抑制剂或GLP-1受体激动剂的特定两试剂组合使用； （c）在已经使用基底胰岛素的受试者中添加奶油胰岛素； （d）用人类胰岛素与模拟胰岛素治疗。分析采用了现代的比较有效性统计方法，包括具有逆概率加权（IPW）的新用户设计和边缘结构建模（MSM）和有针对性的最小损失估计（TMLE），在某些条件下，在某些条件下，可以在某些条件下进行适当的调整，以适应时间依赖性的混杂因素，以便在早期的预期和临床库存之间进行适应性的carsements and Comportias and Atsection and Atsection Batias and Selection and vy Batias。这项研究结果有可能通过识别通常使用通常使用降解葡萄糖的方案来最大程度地提高CV益处并最大程度地减少CV风险的情况，从而可以大大改善数百万型糖尿病的美国人的CV结局。