BACKGROUND Empagliflozin and dapagliflozin have proven cardiovascular benefits in people with type 2 diabetes at high cardiovascular risk, but their comparative effectiveness is unknown. METHODS This study used nationwide, population-based Danish health registries to emulate a hypothetical target trial comparing empagliflozin versus dapagliflozin initiation, in addition to standard care, among people with treated type 2 diabetes from 2014 through 2020. The outcome was a composite of myocardial infarction, ischemic stroke, heart failure (HF), or cardiovascular death (major adverse cardiovascular event). Participants were followed until an outcome, emigration, or death occurred; 6 years after initiation; or December 31, 2021, whichever occurred first. Logistic regression was used to compute inverse probability of treatment and censoring weights, controlling for 57 potential confounders. In intention-to-treat analyses, 6-year adjusted risks, risk differences, and risk ratios, considering noncardiovascular death competing events, were estimated. Analyses were stratified by coexisting atherosclerotic cardiovascular disease and HF. A per-protocol design was performed as a secondary analysis. RESULTS There were 36 670 eligible empagliflozin and 20 606 eligible dapagliflozin initiators. In the intention-to-treat analysis, the adjusted 6-year absolute risk of major adverse cardiovascular event was not different between empagliflozin and dapagliflozin initiators (10.0% versus 10.0%; risk difference, 0.0% [95% CI, -0.9% to 1.0%]; risk ratio, 1.00 [95% CI, 0.91 to 1.11]). The findings were consistent in people with atherosclerotic cardiovascular disease (risk difference, -2.3% [95% CI, -8.2% to 3.5%]; risk ratio, 0.92 [95% CI, 0.74 to 1.14]) and without atherosclerotic cardiovascular disease (risk difference, 0.3% [95% CI, -0.6% to 1.2%]; risk ratio, 1.04 [95% CI, 0.93 to 1.16]) and in people with HF (risk difference, 1.1% [95% CI, -6.5% to 8.6%]; risk ratio, 1.04 [95% CI, 0.79 to 1.37]) and without HF (risk difference, -0.1% [95% CI, -1.0% to 0.8%]; risk ratio, 0.99 [95% CI, 0.90 to 1.09]). The 6-year risks of major adverse cardiovascular event were also not different in the per-protocol analysis (9.1% versus 8.8%; risk difference, 0.2% [95% CI, -2.1% to 2.5%]; risk ratio, 1.03 [95% CI, 0.80 to 1.32]). CONCLUSIONS Empagliflozin and dapagliflozin initiators had no differences in 6-year cardiovascular outcomes in adults with treated type 2 diabetes with or without coexisting atherosclerotic cardiovascular disease or HF.

中文翻译：

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恩格列净与达格列净在接受治疗的 2 型糖尿病成人中的心血管疗效比较：一项靶向试验模拟。


背景 恩格列净和达格列净已证明对心血管风险高的 2 型糖尿病患者有益，但它们的比较效果尚不清楚。方法 本研究使用全国性的、基于人群的丹麦卫生登记处来模拟一项假设的目标试验，该试验比较了 2014 年至 2020 年接受治疗的 2 型糖尿病患者加入恩格列净与达格列净启动以及标准护理。结局是心肌梗死、缺血性卒中、心力衰竭 （HF） 或心血管死亡 （主要不良心血管事件） 的复合结局。对参与者进行随访，直到出现结果、移民或死亡;开始后 6 年;或 2021 年 12 月 31 日，以先发生者为准。使用 Logistic 回归计算治疗的逆概率和删失权重，控制 57 个潜在的混杂因素。在意向治疗分析中，考虑到非心血管死亡竞争事件，估计了 6 年调整后的风险、风险差异和风险比。按共存的动脉粥样硬化性心血管疾病和 HF 对分析进行分层。按照方案设计作为二次分析进行。结果 有 36 670 例符合条件的恩格列净和 20 606 例合格的达格列净引发剂。在意向治疗分析中，恩格列净和达格列净启动剂之间调整后的 6 年主要不良心血管事件绝对风险没有差异（10.0% 对 10.0%;风险差，0.0% [95% CI，-0.9% 至 1.0%];风险比，1.00 [95% CI，0.91 至 1.11]）。动脉粥样硬化性心血管疾病患者的研究结果一致（风险差，-2.3% [95% CI，-8.2% 至 3.5%];风险比，0.92 [95% CI，0.74 至 1]。14]）且无动脉粥样硬化性心血管疾病（风险差，0.3% [95% CI，-0.6% 至 1.2%];风险比，1.04 [95% CI，0.93 至 1.16]），以及 HF 患者（风险差，1.1% [95% CI，-6.5% 至 8.6%];风险比，1.04 [95% CI，0.79 至 1.37]）和无 HF（风险差，-0.1% [95% CI，-1.0% 至 0.8%];风险比， 0.99 [95% CI，0.90 至 1.09]）。在符合方案的分析中，主要不良心血管事件的 6 年风险也没有差异 （9.1% 对 8.8%;风险差，0.2% [95% CI，-2.1% 至 2.5%];风险比，1.03 [95% CI，0.80 至 1.32]）。结论 恩格列净和达格列净引发剂在接受治疗的 2 型糖尿病成人伴或不伴动脉粥样硬化性心血管疾病或 HF 的 6 年心血管结局中无差异。