Background

Receptor selectivity of sodium-glucose cotransporter-2 inhibitors (SGLT2i) varies greatly between agents. The overall improvement of cardiovascular (CV) outcomes in heart failure (HF) patients varies between trials. We, therefore, evaluated the comparative efficacy of individual SGLT2i and the influence of their respective receptor selectivity thereon.

Methods

We identified randomized controlled trials investigating the use of SGLT2i in patients with HF—either as the target cohort or as a subgroup of it. Comparators included placebo or any other active treatment. The primary endpoint was the composite of hospitalization for HF or CV death. Secondary outcomes included all-cause mortality, CV mortality, hospitalization for HF, worsening renal function (RF), and the composite of worsening RF or CV death. Evidence was synthesized using network meta-analysis. In addition, the impact of receptor selectivity on outcomes was analysed using meta-regression.

Results

We identified 18,265 patients included in 22 trials. Compared to placebo, selective and non-selective SGLT2i improved fatal and non-fatal HF events. Head-to-head comparisons suggest superior efficacy with sotagliflozin as compared to dapagliflozin, empagliflozin or ertugliflozin. No significant difference was found between canagliflozin and sotagliflozin. Meta-regression analyses show a decreasing benefit on HF events with increasing receptor selectivity of SGLT2i. In contrast, receptor selectivity did not affect mortality and renal endpoints and no significant difference between individual SGLT2i was noted.

Conclusion

Our data point towards a class-effect of SGLT2i on mortality and renal outcomes. However, non-selective SGLT2i such as sotagliflozin may be superior to highly selective SGLT2i in terms of HF outcomes.

中文翻译：

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受体选择性对 SGLT2 抑制剂对心力衰竭患者益处的影响：系统评价和头对头比较疗效网络荟萃分析

背景

钠-葡萄糖协同转运蛋白 2 抑制剂 (SGLT2i) 的受体选择性因药物而异。心力衰竭 (HF) 患者心血管 (CV) 结局的总体改善因试验而异。因此，我们评估了单个 SGLT2i 的比较功效及其各自受体选择性的影响。

方法

我们确定了调查在 HF 患者中使用 SGLT2i 的随机对照试验——作为目标队列或作为其亚组。比较者包括安慰剂或任何其他积极治疗。主要终点是因 HF 或 CV 死亡而住院的复合终点。次要结局包括全因死亡率、CV 死亡率、因 HF 住院、肾功能恶化 (RF) 以及恶化的 RF 或 CV 死亡的复合。使用网络荟萃分析综合证据。此外，使用元回归分析了受体选择性对结果的影响。

结果

我们在 22 项试验中确定了 18,265 名患者。与安慰剂相比，选择性和非选择性 SGLT2i 改善了致命和非致命 HF 事件。头对头比较表明，与 dapagliflozin、empagliflozin 或 ertugliflozin 相比，使用 sotagliflozin 的疗效更好。卡格列净和索格列净之间没有发现显着差异。Meta 回归分析显示，随着 SGLT2i 受体选择性的增加，对 HF 事件的益处减少。相比之下，受体选择性不影响死亡率和肾脏终点，并且没有注意到个体 SGLT2i 之间的显着差异。

结论

我们的数据表明 SGLT2i 对死亡率和肾脏结局的影响。然而，就 HF 结局而言，非选择性 SGLT2i（如 sotagliflozin）可能优于高选择性 SGLT2i。