Generalizability of Cardiovascular Safety Trials on SGLT2 Inhibitors to the Real World: Implications for Clinical Practice
Generalizability of Cardiovascular Safety Trials on SGLT2 Inhibitors to the Real World: Implications for Clinical Practice
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SGLT2 抑制剂心血管安全性试验在现实世界中的普遍适用性：对临床实践的启示
DOI：
10.1007/s12325-019-01043-z
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发表时间：
2019-10-01
影响因子：
3.8
通讯作者：
Manicardi, Valeria
中科院分区：
文献类型：
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作者：
Nicolucci, Antonio;Candido, Riccardo;Manicardi, Valeria
简介 根据美国食品和药物管理局 (FDA) 关于评估治疗 2 型糖尿病 (T2DM) 的新药的指导意见，已经开展了多项关于钠-葡萄糖协同转运蛋白 2 抑制剂 (SGLT2i) 的心血管结局安全性试验 (CVOT)。这些试验在研究设计和主要终点定义方面表现出相似性，但其资格标准有所不同。本研究的目的是调查 SGLT2i 上的 CVOT 对患有 T2DM 的意大利成年人的普遍性；我们估计了该患者群体中有资格参加 EMPA-REG OUTCOME (empagliflozin)、CANVAS (canagliflozin)、DECLARE-TIMI 58 (dapagliflozin) 和 VERTIS-CV (ertugliflozin) 研究的比例。方法 这项观察性横断面研究在 222 家意大利糖尿病诊所进行。根据已发布的四个 CVOT 患者资格标准，对 2016 年收治的 455,662 名成年 T2DM 患者的数据进行了分析。评估了目前 SGLT2i 在潜在合格患者中的使用情况。结果 在确定的人群中，符合 EMPA-REG OUTCOME 主要资格标准的患者比例为 11.7%，CANVAS 为 29.4%，DECLARE-TIMI 58 为 55.9%，VERTIS-CV 为 12.8%。在符合这些 CVOT 资格的患者中，只有少数（范围 4.4-6.8%）实际上接受了 SGLT2i 处方。与CVOT中的患者相比，现实世界中符合条件的患者年龄较大、糖尿病病程较长、BMI和HbA1c水平较低、既定心脑血管疾病患病率较低、微血管并发症和外周动脉疾病发生率较高。结论 可能符合 SGLT2i 治疗条件的患者百分比有所不同，这反映了试验中采用的不同资格标准。许多原本可以从 SGLT2i 中获益的患者，不仅可以从心血管保护角度获益，还可以从肾脏保护角度受益，但他们却没有接受治疗。资助阿斯利康。
Introduction Following the US Food and Drug Administration (FDA) guidance on the evaluation of novel agents for the treatment of type 2 diabetes mellitus (T2DM), a number of cardiovascular outcomes safety trials (CVOTs) on sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been conducted. These trials show similarities in study design and definition of primary endpoints, but differ in their eligibility criteria. The aim of the present study was to investigate the generalizability of CVOTs on SGLT2i to Italian adults with T2DM; we estimated the proportions of this patient population who would be eligible for enrollment in EMPA-REG OUTCOME (empagliflozin), CANVAS (canagliflozin), DECLARE-TIMI 58 (dapagliflozin), and VERTIS-CV (ertugliflozin) studies. Methods This observational, cross-sectional study was conducted in 222 Italian diabetes clinics. Data on 455,662 adult patients with T2DM seen during 2016 were analyzed against the published patient eligibility criteria for the four CVOTs. The current use of SGLT2i in potentially eligible patients was assessed. Results Among the population identified, the proportion of patients meeting major eligibility criteria was 11.7% for EMPA-REG OUTCOME, 29.4% for CANVAS, 55.9% for DECLARE-TIMI 58, and 12.8% for VERTIS-CV. Of the patients eligible for these CVOTs, only a minority (range 4.4-6.8%) was actually prescribed an SGLT2i. Compared with patients in the CVOTs, eligible patients in the real world showed older age and longer diabetes duration, lower BMI and HbA1c levels, lower prevalence of established cardiovascular and cerebrovascular disease, and higher rates of microvascular complications and peripheral arterial disease. Conclusion The percentage of patients potentially eligible for treatment with SGLT2i varies as a reflection of different eligibility criteria applied in the trials. A large number of patients that could benefit from SGLT2i in terms of not only cardiovascular protection but also renal protection do not receive the treatment. Funding AstraZeneca.