Departments of Clinical Epidemiology (K.B., U.H.-J., D.H.C., L.P., R.W.T., M.S.), Aarhus University Hospital, Denmark.
Department of Clinical Medicine, Aarhus University, Denmark (K.B., U.H.-J., D.H.C., L.P., R.W.T., M.S.).
Circulation. 2024 Oct 29;150(18):1401-1411. doi: 10.1161/CIRCULATIONAHA.124.068613. Epub 2024 Aug 29.
Empagliflozin and dapagliflozin have proven cardiovascular benefits in people with type 2 diabetes at high cardiovascular risk, but their comparative effectiveness is unknown.
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.
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]).
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.
恩格列净和达格列净已被证明可降低心血管风险较高的 2 型糖尿病患者的心血管风险，但它们的疗效比较尚不清楚。
本研究利用全国性的丹麦基于人群的健康登记处，模拟了一项假设性的目标试验，比较了恩格列净与达格列净在 2014 年至 2020 年期间接受治疗的 2 型糖尿病患者中的起始治疗，外加标准治疗。主要复合终点为心肌梗死、缺血性卒中和心力衰竭（HF）或心血管死亡（主要不良心血管事件）。在出现结局、移民或死亡；起始治疗后 6 年；或 2021 年 12 月 31 日，以先发生者为准，对参与者进行随访。采用 logistic 回归计算逆概率治疗和删失权重，控制了 57 个潜在混杂因素。在意向治疗分析中，考虑到非心血管死亡的竞争事件，估计了 6 年的调整风险、风险差异和风险比。按照是否存在动脉粥样硬化性心血管疾病和 HF 进行分层分析。作为次要分析，进行了符合方案设计分析。
共纳入 36670 名恩格列净和 20606 名达格列净起始治疗的合格患者。在意向治疗分析中，恩格列净和达格列净起始治疗患者的 6 年主要不良心血管事件的绝对风险无差异（10.0%比 10.0%；风险差异，0.0%[95%CI，-0.9%至 1.0%]；风险比，1.00[95%CI，0.91 至 1.11]）。在有动脉粥样硬化性心血管疾病（风险差异，-2.3%[95%CI，-8.2%至 3.5%]；风险比，0.92[95%CI，0.74 至 1.14]）和无动脉粥样硬化性心血管疾病（风险差异，0.3%[95%CI，-0.6%至 1.2%]；风险比，1.04[95%CI，0.93 至 1.16]）以及有 HF（风险差异，1.1%[95%CI，-6.5%至 8.6%]；风险比，1.04[95%CI，0.79 至 1.37]）和无 HF（风险差异，-0.1%[95%CI，-1.0%至 0.8%]；风险比，0.99[95%CI，0.90 至 1.09]）的患者中，这一发现也是一致的。在符合方案分析中，主要不良心血管事件的 6 年风险也无差异（9.1%比 8.8%；风险差异，0.2%[95%CI，-2.1%至 2.5%]；风险比，1.03[95%CI，0.80 至 1.32]）。
在伴有或不伴有并存的动脉粥样硬化性心血管疾病或 HF 的接受治疗的 2 型糖尿病成人中，恩格列净和达格列净起始治疗 6 年内的心血管结局没有差异。
