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

项目摘要/摘要 2型糖尿病(T2D)患者患动脉粥样硬化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后果，如终末期肾脏疾病 (ESRD)。因此，在T2D人群中减少这些不良健康事件的策略至关重要 很重要。与罗格列酮相关的心血管安全问题导致食品和药物管理局(FDA) 要求对新的降糖疗法进行心血管结果试验。心血管结局试验 关于最近推出的两类降糖药物，钠葡萄糖转运蛋白2(SGLT2)抑制剂 而胰升糖素样肽1(GLP-1)受体激动剂出人意料地显示出对心血管的好处 降低心肌梗死、中风、心力衰竭和肾脏结局的比率，特别是在那些患有 建立了ASCVD。结果，FDA批准了三种SGLT-2抑制剂的新适应症(依帕格列酮， 和三种GLP-1受体激动剂(利拉鲁肽、度那路肽和赛马路德)治疗 T2D和ASCVD患者心血管事件的减少。然而，心血管疾病 这些新型糖尿病药物在T2D中的疗效仅在非常高的ASCVD的背景下进行评估 风险和AS作为标准T2D治疗的附加治疗。通过更广泛地使用这些昂贵的新药 取代更便宜的标准药物方案可能会对临床结果和成本产生不确定的影响 病人和医疗系统。我们提出了一种决策分析方法来比较长期临床和 以指南为基础的和替代治疗算法的经济结果，并确定最佳战略 使用SGLT2抑制剂和GLP-1受体激动剂。保险覆盖范围和费用分担可能会影响获取 和对这些制剂的依从性，因此我们将额外评估它们的使用的经济影响 从患者的角度出发，解决在利用率和成本效益方面的潜在差异 不同心血管风险水平的T2D患者。我们的具体目标是评估长期的差异 使用新型糖尿病药物的策略与结合Meta-Me的传统治疗策略的临床结果 用流行病学数据的预测和模拟建模对重建的试验生存数据进行分析。第一, 我们将比较以指南为基础的新型糖尿病药物作为二线治疗与替代治疗的策略 策略包括在不同目标患者人群中一线使用和联合治疗。第二, 我们将评估这些不同策略在生命质量调整后的存活率和成本方面的差异。 以普遍接受的社会成本效益护理基准为标准的新型糖尿病药物 并解决保险覆盖范围和费用分担对治疗决定的影响。因此，我们的研究将 严格评估预防高血压的新药理学方法的临床价值和成本影响 T2D患者的ASCVD、心力衰竭和肾脏转归。确定符合以下条件的最佳预防策略 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。

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.