Sodium–glucose co-transporter-2 (SGLT2) inhibitors have been studied in patients with heart failure, type 2 diabetes, chronic kidney disease, atherosclerotic cardiovascular disease, and acute myocardial infarction. Individual trials were powered to study composite outcomes in one disease state. We aimed to evaluate the treatment effect of SGLT2 inhibitors on specific clinical endpoints across multiple demographic and disease subgroups. In this systematic review and meta-analysis, we queried online databases (PubMed, Cochrane CENTRAL, and SCOPUS) up to Feb 10, 2024, for primary and secondary analyses of large trials (n>1000) of SGLT2 inhibitors in patients with heart failure, type 2 diabetes, chronic kidney disease, and atherosclerotic cardiovascular disease (including acute myocardial infarction). Outcomes studied included composite of first hospitalisation for heart failure or cardiovascular death, first hospitalisation for heart failure, cardiovascular death, total (first and recurrent) hospitalisation for heart failure, and all-cause mortality. Effect sizes were pooled using random-effects models. This study is registered with PROSPERO, CRD42024513836. We included 15 trials (N=100 952). Compared with placebo, SGLT2 inhibitors reduced the risk of first hospitalisation for heart failure by 29% in patients with heart failure (hazard ratio [HR] 0·71 [95% CI 0·67–0·77]), 28% in patients with type 2 diabetes (0·72 [0·67–0·77]), 32% in patients with chronic kidney disease (0·68 [0·61–0·77]), and 28% in patients with atherosclerotic cardiovascular disease (0·72 [0·66–0·79]). SGLT2 inhibitors reduced cardiovascular death by 14% in patients with heart failure (HR 0·86 [95% CI 0·79–0·93]), 15% in patients with type 2 diabetes (0·85 [0·79–0·91]), 11% in patients with chronic kidney disease (0·89 [0·82–0·96]), and 13% in patients with atherosclerotic cardiovascular disease (0·87 [0·78–0·97]). The benefit of SGLT2 inhibitors on both first hospitalisation for heart failure and cardiovascular death was consistent across the majority of the 51 subgroups studied. Notable exceptions included acute myocardial infarction (22% reduction in first hospitalisation for heart failure; no effect on cardiovascular death) and heart failure with preserved ejection fraction (26% reduction in first hospitalisation for heart failure; no effect on cardiovascular death). SGLT2 inhibitors reduced heart failure events and cardiovascular death in patients with heart failure, type 2 diabetes, chronic kidney disease, and atherosclerotic cardiovascular disease. These effects were consistent across a wide range of subgroups within these populations. This supports the eligibility of a large population with cardiorenal-metabolic diseases for treatment with SGLT2 inhibitors. None.

中文翻译：

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SGLT2 抑制剂对心脏代谢疾病谱中心力衰竭结局和心血管死亡的影响：系统评价和荟萃分析


钠-葡萄糖协同转运蛋白 2 （SGLT2） 抑制剂已在心力衰竭、2 型糖尿病、慢性肾病、动脉粥样硬化性心血管疾病和急性心肌梗死患者中进行了研究。单个试验用于研究一种疾病状态下的复合结局。我们旨在评估 SGLT2 抑制剂对多个人口统计学和疾病亚组特定临床终点的治疗效果。在本系统综述和荟萃分析中，我们查询了截至 2024 年 2 月 10 日的在线数据库（PubMed、Cochrane CENTRAL 和 SCOPUS），以对心力衰竭、2 型糖尿病、慢性肾病和动脉粥样硬化性心血管疾病（包括急性心肌梗死）患者使用 SGLT2 抑制剂的大型试验 （n>1000） 进行初级和次级分析。研究的结局包括因心力衰竭或心血管死亡首次住院、因心力衰竭首次住院、心血管死亡、因心力衰竭而总（首次和复发）住院以及全因死亡率的复合结局。使用随机效应模型合并效应大小。这项研究已在 CRD42024513836 PROSPERO 注册。我们纳入了 15 项试验 （N=100 952）。与安慰剂相比，SGLT2 抑制剂使心力衰竭患者首次因心力衰竭住院的风险降低了 29%（风险比 [HR] 0·71 [95% CI 0·67–0·77]），2 型糖尿病患者降低了 28% （0·72 [0·67–0·77]），慢性肾病患者降低了 32% （0·68 [0·61–0·77]）， 动脉粥样硬化性心血管疾病患者为 28% （0·72 [0·66–0·79]）。 SGLT2 抑制剂使心力衰竭患者的心血管死亡率降低了 14% （HR 0·86 [95% CI 0·79–0·93]），2 型糖尿病患者降低了 15% （0·85 [0·79–0·91]），慢性肾病患者降低了 11% （0·89 [0·82–0·96]），动脉粥样硬化性心血管疾病患者降低了 13% （0·87 [0·78–0·97]）。SGLT2 抑制剂对心力衰竭首次住院和心血管死亡的益处在所研究的 51 个亚组中的大多数中是一致的。值得注意的例外包括急性心肌梗死（因心力衰竭首次住院治疗减少 22%，对心血管死亡没有影响）和射血分数保留的心力衰竭（因心力衰竭首次住院减少 26%，对心血管死亡没有影响）。SGLT2 抑制剂减少了心力衰竭、2 型糖尿病、慢性肾病和动脉粥样硬化性心血管疾病患者的心力衰竭事件和心血管死亡。这些影响在这些人群中的广泛亚组中是一致的。这支持了大量患有心肾代谢疾病的人群有资格接受 SGLT2 抑制剂治疗。没有。