Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.
Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Lancet Diabetes Endocrinol. 2024 Jul;12(7):447-461. doi: 10.1016/S2213-8587(24)00102-5. Epub 2024 May 17.
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.
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钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂已在心力衰竭、2 型糖尿病、慢性肾脏病、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。各个试验都有能力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的特定临床终点的治疗效果。
在这项系统评价和荟萃分析中，我们在 2024 年 2 月 10 日之前在在线数据库（PubMed、Cochrane CENTRAL 和 SCOPUS）中查询了大型 SGLT2 抑制剂试验（n＞1000）的主要和次要分析，这些试验涉及心力衰竭、2 型糖尿病、慢性肾脏病和动脉粥样硬化性心血管疾病（包括急性心肌梗死）患者。研究的结局包括心力衰竭或心血管死亡的首次住院的复合结局、心力衰竭的首次住院、心血管死亡、心力衰竭的总（首次和复发）住院和全因死亡率。使用随机效应模型汇总效应大小。这项研究在 PROSPERO 注册，CRD42024513836。
我们纳入了 15 项试验（n=100952）。与安慰剂相比，SGLT2 抑制剂使心力衰竭患者心力衰竭的首次住院风险降低了 29%（风险比[HR]0.71[95%CI0.67-0.77]），2 型糖尿病患者降低了 28%（0.72[0.67-0.77]），慢性肾脏病患者降低了 32%（0.68[0.61-0.77]），动脉粥样硬化性心血管疾病患者降低了 28%（0.72[0.66-0.79]）。SGLT2 抑制剂使心力衰竭患者的心血管死亡风险降低了 14%（HR0.86[95%CI0.79-0.93]），2 型糖尿病患者降低了 15%（0.85[0.79-0.91]），慢性肾脏病患者降低了 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 抑制剂在心力衰竭和心血管死亡方面的获益在研究的 51 个大多数亚组中是一致的。值得注意的例外包括急性心肌梗死（心力衰竭首次住院的 22%减少；对心血管死亡没有影响）和射血分数保留的心力衰竭（心力衰竭首次住院的 26%减少；对心血管死亡没有影响）。
SGLT2 抑制剂降低了心力衰竭、2 型糖尿病、慢性肾脏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。这些效果在这些人群的广泛亚组中是一致的。这支持了患有心脏肾代谢疾病的大量人群有资格接受 SGLT2 抑制剂治疗。
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