Division of Cardiology, St. Michael's Hospital, University of Toronto, 30 Bond Street, Toronto, Ontario M5B 1W8, Canada.
Section of Endocrinology, Yale School of Medicine, 333 Cedar St, New Haven, CT 06520, USA.
Eur Heart J. 2020 Jan 7;41(2):209-217. doi: 10.1093/eurheartj/ehz621.
Hypoglycaemia, in patients with Type 2 diabetes (T2D) is associated with an increased risk for cardiovascular (CV) events. In EMPA-REG OUTCOME, the sodium-glucose co-transporter-2 inhibitor empagliflozin reduced the risk of CV death by 38% and heart failure hospitalization (HHF) by 35%, while decreasing glycated haemoglobin (HbA1c) without increasing hypoglycaemia. We investigated CV outcomes in patients with hypoglycaemia during the trial and the impact of hypoglycaemia on the treatment effect of empagliflozin.
About 7020 patients with T2D (HbA1c 7-10%) were treated with empagliflozin 10 or 25 mg, or placebo and followed for median 3.1 years. The relationship between on-trial hypoglycaemia and CV outcomes, and effects of empagliflozin on outcomes by incident hypoglycaemia [HYPO-broad: symptomatic hypoglycaemia with plasma glucose (PG) ≤70 mg/dL, any hypoglycaemia with PG <54 mg/dL, or severe hypoglycaemia, and HYPO-strict: hypoglycaemia with PG <54 mg/dL, or severe hypoglycaemia] was investigated using adjusted Cox regression models with time-varying covariates for hypoglycaemia and interaction with treatment. HYPO-broad occurred in 28% in each group and HYPO-strict in 19%. In the placebo group, hypoglycaemia was associated with an increased risk of HHF for both HYPO-broad [hazard ratio (HR, 95% confidence interval, CI) 1.91 (1.25-2.93)] and HYPO-strict [1.72 (1.06-2.78)]. HYPO-broad (but not HYPO-strict) was associated with an increased risk of myocardial infarction (MI) [HR 1.56 (1.06-2.29)]. Empagliflozin improved CV outcomes, regardless of occurrence of hypoglycaemia (P-for interactions >0.05).
In this post hoc exploratory analysis, hypoglycaemia was associated with an increased risk of HHF and MI. Hypoglycaemia risk was not increased with empagliflozin and incident hypoglycaemia did not attenuate its cardio-protective effects.
2 型糖尿病（T2D）患者的低血糖与心血管（CV）事件风险增加相关。在 EMPA-REG OUTCOME 试验中，钠-葡萄糖共转运蛋白 2 抑制剂恩格列净降低了 38%的 CV 死亡风险和 35%的心衰住院（HHF）风险，同时降低了糖化血红蛋白（HbA1c）而不增加低血糖。我们研究了试验期间发生低血糖的患者的 CV 结局以及低血糖对恩格列净治疗效果的影响。
约 7020 名 T2D 患者（HbA1c 7-10%）接受恩格列净 10 或 25mg 或安慰剂治疗，中位随访 3.1 年。使用调整后的 Cox 回归模型，根据时间变化的低血糖协变量和治疗的交互作用，研究了试验期间低血糖与 CV 结局之间的关系，以及恩格列净对结局的影响[低血糖广泛定义：血糖（PG）≤70mg/dL 的症状性低血糖，PG<54mg/dL 的任何低血糖或严重低血糖，低血糖严格定义：PG<54mg/dL 的低血糖或严重低血糖]。每组中低血糖广泛定义的发生率为 28%，低血糖严格定义的发生率为 19%。在安慰剂组中，低血糖与 HHF 的风险增加相关，低血糖广泛定义的 HR（95%CI）为 1.91（1.25-2.93），低血糖严格定义的 HR 为 1.72（1.06-2.78）。低血糖广泛定义（而非低血糖严格定义）与心肌梗死（MI）的风险增加相关[HR 1.56（1.06-2.29）]。无论是否发生低血糖，恩格列净均改善了 CV 结局（P-交互作用>0.05）。
在这项事后探索性分析中，低血糖与 HHF 和 MI 的风险增加相关。恩格列净不会增加低血糖风险，且低血糖的发生并未减弱其心脏保护作用。
Zotero 插件
