Clinical and economic value of novel diabetes medications for prevention of cardiovascular disease in type 2 diabetes

新型糖尿病药物预防 2 型糖尿病心血管疾病的临床和经济价值

• 批准号: 10621154
• 负责人: Bart Ferket
• 金额: $ 68.45万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10621154
• 关键词: Address; Adherence; Adoption; Adult; Affect; Agonist; Algorithms; American; Amputation; Atherosclerosis; Benchmarking; Cardiovascular system; Caring; Cause of Death; Cessation of life; Chronic Kidney Failure; Clinical; Clinical Practice Guideline; Combined Modality Therapy; Cost Sharing; Data; Diabetes Mellitus; Diabetic Ketoacidosis; Disparity; End stage renal failure; Epidemiology; Evaluation; Event; Fracture; GLP-I receptor; Glucose; Glucose Transporter; Glycosylated hemoglobin A; Goals; Guidelines; Health; Health system; Heart failure; Hospitalization; Individual; Insurance Coverage; Kidney; Kidney Diseases; Knee; Measures; Medical; Meta-Analysis; Metformin; Myocardial Infarction; Non-Insulin-Dependent Diabetes Mellitus; Outcome; Patient Representative; Patients; Pharmaceutical Preparations; Population; Prevention approach; Prevention strategy; Public Health; Recommendation; Regimen; Renal function; Research; Research Project Grants; Safety; Serious Adverse Event; Sodium; Stroke; Translating; United States Food and Drug Administration; Woman; adverse drug reaction; alternative treatment; atherosclerosis risk; cardiovascular disorder prevention; cardiovascular disorder risk; cardiovascular risk factor; clinical practice; cohort; comparative cost effectiveness; cost; cost effective; cost effectiveness; diabetes mellitus therapy; drug standard; economic cost; economic implication; economic outcome; economic value; effectiveness outcome; epidemiologic data; genital infection; improved; inhibitor; innovation; liraglutide; men; models and simulation; mortality; novel; novel strategies; patient population; patient subsets; pharmacologic; prescription drug costs; prognostic; randomized trial; randomized, controlled study; rosiglitazone; secondary endpoint; simulation; symporter; treatment strategy

PROJECT SUMMARY/ABSTRACT Individuals with type 2 diabetes (T2D) are at substantially increased risk for atherosclerotic cardiovascular disease (ASCVD) and heart failure, as well as other important outcomes such as end-stage renal disease (ESRD). Therefore, strategies to reduce these adverse health events in the T2D population are critically important. Cardiovascular safety concerns related to rosiglitazone led the Food and Drug Administration (FDA) to mandate cardiovascular outcome trials for new glucose lowering therapies. The cardiovascular outcome trials on two recently introduced glucose lowering classes of drugs, sodium glucose transporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists unexpectedly showed cardiovascular benefits with reduced rates of myocardial infarction, stroke, heart failure, and renal outcomes, particularly in those with established ASCVD. As a result, the FDA approved a new indication for three SGLT-2 inhibitors (empagliflozin, canagliflozin and dapagliflozin) and three GLP-1 receptor agonists (liraglutide, dulaglutide and semaglutide) for reduction of cardiovascular events in those with T2D and established ASCVD. However, cardiovascular outcomes of these novel diabetes agents in T2D have only been evaluated in the context of very high ASCVD risk and as add-on treatment to standard T2D therapy. Wider use of these expensive novel medications by replacing cheaper standard drug regimens may yield uncertain effects on clinical outcomes and costs to the patient and the health system. We propose a decision-analytic approach to compare long-term clinical and economic outcomes of guideline-based and alternative treatment algorithms and identify optimal strategies for the use of SGLT2 inhibitors and GLP-1 receptor agonists. Insurance coverage and cost sharing can affect access and adherence to these agents and we will therefore additionally evaluate economic implications of their use from a patient perspective and address the potential disparities in utilization and cost-effectiveness across patients with T2D at different cardiovascular risk levels. Our specific aims are to assess differences in long-term clinical outcomes of strategies utilizing novel diabetes medications vs conventional care by combining meta- analysis of reconstructed trial survival data with prognostic and simulation modeling of epidemiologic data. First, we will compare guideline-based strategies of novel diabetes medication as second-line therapy vs alternative strategies including first-line usage and combination therapy across different target patient populations. Second, we will evaluate differences in lifetime quality-adjusted survival and costs of these various strategies utilizing novel diabetes medication with generally accepted societal benchmarks for cost-effective care as the criterion and address the impact of insurance coverage and cost sharing on treatment decisions. Thus, our research will rigorously evaluate clinical value and cost implications of novel pharmacologic approaches to prevention of ASCVD, heart failure and renal outcomes in patients with T2D. Identifying optimal prevention strategies that are economically sensible has the potential to improve public health in a cost-effective manner.

项目总结/摘要 2型糖尿病（T2 D）患者发生动脉粥样硬化性心血管疾病的风险显著增加 疾病（ASCVD）和心力衰竭，以及其他重要结局，如终末期肾病 （ESRD）。因此，减少T2 D人群中这些不良健康事件的策略至关重要。 重要.美国食品药品监督管理局（FDA） 要求对新的降糖疗法进行心血管结局试验。心血管结局试验 最近推出的两种降糖药物，钠葡萄糖转运蛋白2（SGLT 2）抑制剂， 和胰高血糖素样肽1（GLP-1）受体激动剂意外地显示出心血管益处， 降低心肌梗死、卒中、心力衰竭和肾脏结局的发生率，特别是在那些 建立ASCVD。因此，FDA批准了三种SGLT-2抑制剂的新适应症（恩格列净， 卡格列净和达格列净）和三种GLP-1受体激动剂（利拉鲁肽、度乐肽和Semaglutide）， 减少T2 D和确诊ASCVD患者的心血管事件。然而，心血管 这些新型糖尿病药物治疗T2 D的结局仅在非常高的ASCVD背景下进行了评价 作为标准T2 D治疗的附加治疗。这些昂贵的新型药物的广泛使用， 替代更便宜的标准药物方案可能会对临床结果产生不确定的影响， 患者和卫生系统。我们提出了一种决策分析方法来比较长期的临床和 基于指南和替代治疗算法的经济结果，并确定最佳策略， SGLT 2抑制剂和GLP-1受体激动剂的使用。保险覆盖和费用分摊可能影响获得 因此，我们将额外评估其使用的经济影响 从患者的角度，并解决利用率和成本效益的潜在差异， 处于不同心血管风险水平的T2 D患者。我们的具体目标是评估长期 通过结合Meta，使用新型糖尿病药物与传统护理策略的临床结局 用流行病学数据的预测和模拟模型分析重建的试验生存数据。第一、 我们将比较新型糖尿病药物作为二线治疗与替代治疗的指南策略 包括一线使用和不同目标患者人群的联合治疗策略。第二、 我们将评估这些不同策略在终生质量调整生存率和成本方面的差异， 新型糖尿病药物，以普遍接受的成本效益护理社会基准为标准 并解决保险范围和费用分摊对治疗决定的影响。我们的研究将 严格评估新的药理学方法的临床价值和成本影响，以预防 T2 D患者的ASCVD、心力衰竭和肾脏结局。确定最佳预防战略， 经济上合理的做法有可能以具有成本效益的方式改善公共卫生。

项目成果

Cardiovascular and Renal Benefits of Novel Diabetes Drugs by Baseline Cardiovascular Risk: A Systematic Review, Meta-analysis, and Meta-regression.

新型糖尿病药物对心血管和肾脏的益处（按基线心血管风险划分）：系统评价、荟萃分析和荟萃回归。

• DOI: 10.2337/dc22-0772
• 发表时间: 2023
• 期刊: Diabetes care
• 影响因子: 16.2
• 作者: Rodriguez-Valadez,JoséM;Tahsin,Malak;Fleischmann,KirstenE;Masharani,Umesh;Yeboah,Joseph;Park,Meyeon;Li,Lihua;Weber,Ellerie;Li,Yan;Berkalieva,Asem;Max,Wendy;Hunink,MGMyriam;Ferket,BartS
• 通讯作者: Ferket,BartS