Background and Aims Individuals with heart failure (HF), other forms of cardiovascular disease, or kidney disease are at increased risk for the development and adverse health effects of diabetes. As such, prevention or delay of diabetes is an important treatment priority in these groups. The aim of this meta-analysis was to determine the effect of sodium-glucose co-transporter 2 inhibitors (SGLT2i) on incident diabetes in HF across the spectrum of left ventricular ejection fraction (LVEF) and across the broader spectrum of cardiovascular or kidney disease. Methods First, the effects of dapagliflozin vs. placebo on new-onset diabetes were assessed in a pooled, participant-level analysis of the DAPA-HF and DELIVER trials. New-onset diabetes was defined as the new initiation of glucose-lowering therapy during follow-up, and time from randomization to new-onset diabetes was evaluated using Cox proportional hazards models. Second, PubMed and Embase were searched to identify large-scale randomized clinical outcomes trials (RCTs) comparing SGLT2i with placebo among adults with cardiovascular or kidney disease. A trial-level meta-analysis was then conducted to summarize the treatment effects of SGLT2i on the incidence of new-onset diabetes. Results In the pooled analysis of DAPA-HF and DELIVER including 5623 participants with HF but without diabetes at baseline, dapagliflozin reduced the incidence of new-onset diabetes by 33% [hazard ratio (HR), 0.67; 95% confidence interval (CI), .49–.91; P = .012] when compared with placebo. There was no evidence of heterogeneity across the spectrum of continuous LVEF or key subgroups. Among seven complementary RCTs including 17 855 participants with cardiovascular or kidney disease, SGLT2i reduced the of new-onset diabetes by 26% (HR, 0.74; 95% CI .65–.85; P < .001), with consistent effects across trials. Conclusions SGLT2i reduced the incidence of new-onset diabetes among individuals with cardiovascular or kidney disease. These findings suggest that SGLT2i implementation may have an important ancillary benefit on prevention or delay of diabetes in these high-risk populations.

中文翻译：

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钠-葡萄糖协同转运蛋白 2 抑制剂和心血管或肾脏疾病中新发糖尿病


背景和目标 患有心力衰竭 （HF）、其他形式的心血管疾病或肾脏疾病的个体患糖尿病和对健康的不利影响的风险增加。因此，预防或延缓糖尿病是这些群体的重要治疗重点。本荟萃分析的目的是确定钠-葡萄糖协同转运蛋白 2 抑制剂 （SGLT2i） 对左心室射血分数 （LVEF） 范围和更广泛的心血管或肾脏疾病的 HF 新发糖尿病的影响。方法 首先，在 DAPA-HF 和 DELIVER 试验的汇总参与者水平分析中评估达格列净与安慰剂对新发糖尿病的影响。新发糖尿病定义为随访期间新开始降糖治疗，并使用 Cox 比例风险模型评估从随机分组到新发糖尿病的时间。其次，检索 PubMed 和 Embase，以确定在成人心血管或肾脏疾病患者中比较 SGLT2i 与安慰剂的大规模随机临床结局试验 （RCT）。然后进行试验水平的荟萃分析，总结 SGLT2i 对新发糖尿病发病率的治疗效果。结果 在 DAPA-HF 和 DELIVER 的汇总分析中，包括 5623 名 HF 但基线时没有糖尿病的参与者，达格列净将新发糖尿病的发生率降低了 33% [风险比 （HR），0.67;95% 置信区间 （CI），.49–.91;P = .012]。没有证据表明连续 LVEF 或关键亚组的范围存在异质性。在包括 17 855 名心血管或肾脏疾病参与者的 7 项补充 RCT 中，SGLT2i 将新发糖尿病的发生率降低了 26% （HR，0.74;95% CI .65–.85;P < .001），在试验中具有一致的效果。结论 SGLT2i 降低了心血管或肾脏疾病患者新发糖尿病的发生率。这些发现表明，SGLT2i 的实施可能对这些高危人群的糖尿病预防或延迟具有重要的辅助益处。