Diabetic patients frequently develop heart failure with preserved (HFpEF) or mid-range (HFmEF) cardiac ejection fractions. This condition may be secondary to diabetic cardiomyopathy or one of several relevant comorbidities, mainly hypertension. Several mechanisms link diabetes to HFpEF or HFmEF. Among these, non-enzymatic glycation of interstitial proteins, lipotoxicity, and endothelial dysfunction may promote structural damage and ultimate lead to heart failure. Findings from several large-scale trials indicated that treatment with sodium/glucose cotransporter 2 inhibitors (SGLT2-iss) resulted in significant improvements in cardiovascular outcomes in diabetic patients with high cardiovascular risk. However, there is currently some evidence that suggests a clinical advantage of using SGLT2-iss specifically in cases of HFpEF or HFmEF. Preclinical and clinical studies revealed that SGLT2-iss treatment results in a reduction in left ventricular mass and improved diastolic function. While some of the beneficial effects of SGLT2-iss have already been characterized (e.g., increased natriuresis and diuresis as well as reduced blood pressure, plasma volume, and arterial stiffness, and nephron-protective activities), there is increasing evidence suggesting that SGLT2-iss may have direct actions on the heart. These findings include SGLT2-iss-mediated reductions in the expression of hypertrophic foetal genes and diastolic myofilaments stiffness, increases in global phosphorylation of myofilament regulatory proteins (in HFpEF), inhibition of cardiac late sodium channel current and Na⁺/H⁺ exchanger activity, metabolic shifts, and effects on calcium cycling. Preliminary data from previously published studies suggest that SGLT2-iss could be useful for the treatment of HFpEF and HFmEF. Several large ongoing trials, including DELIVER AND EMPEROR -preserved have been designed to evalute the efficacy of SGLT2-iss in improving clinical outcomes in patients diagnosed with HFpEF. The goal of this manuscript is to review the use of SGLT2-iss inhibitors for HFpEF or HFmEF associated with diabetes.

糖尿病患者经常发生心脏射血分数保留 (HFpEF) 或中等 (HFmEF) 的心力衰竭。这种情况可能继发于糖尿病性心肌病或几种相关合并症之一，主要是高血压。几种机制将糖尿病与 HFpEF 或 HFmEF 联系起来。其中，间质蛋白的非酶促糖化、脂毒性和内皮功能障碍可能促进结构损伤并最终导致心力衰竭。几项大规模试验的结果表明，钠/葡萄糖协同转运蛋白 2 抑制剂 (SGLT2-iss) 治疗可显着改善心血管高危糖尿病患者的心血管结局。然而，目前有一些证据表明，特别是在 HFpEF 或 HFmEF 病例中使用 SGLT2-iss 具有临床优势。临床前和临床研究表明，SGLT2-iss 治疗可减少左心室质量并改善舒张功能。虽然 SGLT2-iss 的一些有益作用已经得到表征（例如，增加尿钠排泄和利尿作用以及降低血压、血浆容量和动脉僵硬度以及肾单位保护活性），但越来越多的证据表明 SGLT2- iss 可能对心脏有直接作用。这些发现包括 SGLT2-iss 介导的肥大胎儿基因表达和舒张期肌丝硬度的降低、肌丝调节蛋白（HFpEF 中）的整体磷酸化增加、心脏晚期钠通道电流和 Na 虽然 SGLT2-iss 的一些有益作用已经得到表征（例如，增加尿钠排泄和利尿作用以及降低血压、血浆容量和动脉僵硬度以及肾单位保护活性），但越来越多的证据表明 SGLT2- iss 可能对心脏有直接作用。这些发现包括 SGLT2-iss 介导的肥大胎儿基因表达和舒张期肌丝硬度的降低、肌丝调节蛋白（HFpEF 中）的整体磷酸化增加、心脏晚期钠通道电流和 Na 虽然 SGLT2-iss 的一些有益作用已经得到表征（例如，增加尿钠排泄和利尿作用以及降低血压、血浆容量和动脉僵硬度以及肾单位保护活性），但越来越多的证据表明 SGLT2- iss 可能对心脏有直接作用。这些发现包括 SGLT2-iss 介导的肥大胎儿基因表达和舒张期肌丝硬度的降低、肌丝调节蛋白（HFpEF 中）的整体磷酸化增加、心脏晚期钠通道电流和 Na 越来越多的证据表明 SGLT2-iss 可能对心脏有直接作用。这些发现包括 SGLT2-iss 介导的肥大胎儿基因表达和舒张期肌丝硬度的降低、肌丝调节蛋白（HFpEF 中）的整体磷酸化增加、心脏晚期钠通道电流和 Na 越来越多的证据表明 SGLT2-iss 可能对心脏有直接作用。这些发现包括 SGLT2-iss 介导的肥大胎儿基因表达和舒张期肌丝硬度的降低、肌丝调节蛋白（HFpEF 中）的整体磷酸化增加、心脏晚期钠通道电流和 Na⁺ /H ⁺交换器活性、代谢变化和对钙循环的影响。先前发表的研究的初步数据表明，SGLT2-iss 可用于治疗 HFpEF 和 HFmEF。几项正在进行的大型试验，包括 DELIVER 和 EMPEROR -preserved，旨在评估 SGLT2-iss 在改善 HFpEF 患者临床结局方面的疗效。本手稿的目的是审查 SGLT2-iss 抑制剂在与糖尿病相关的 HFpEF 或 HFmEF 中的应用。