Teragawa Hiroki, Tanaka Atsushi, Takahashi Kanae, Oshita Chikage, Uchimura Yuko, Kamei Nozomu, Hirai Hiroyuki, Shimabukuro Michio, Taguchi Isao, Okada Yosuke, Node Koichi
Department of Cardiovascular Medicine, JR Hiroshima Hospital, Hiroshima, Japan.
Department of Cardiovascular Medicine, Saga University, Saga, Japan.
Cardiovasc Diabetol. 2025 May 2;24(1):190. doi: 10.1186/s12933-025-02745-1.
Sodium-glucose co-transporter 2 (SGLT2) inhibitors are important for treating patients with preserved left ventricular (LV) ejection fraction (LVEF). Several studies have assessed the effects of SGLT2 inhibitors on LV diastolic function, with conflicting results. In this sub-analysis of the Program of Ipragliflozin for Endothelial Dysfunction in Chronic Kidney Disease and Type 2 Diabetes (PROCEED) trial-including patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD)-we examined the effect of ipragliflozin compared with non-SGLT2 inhibitor standard therapy (control) on changes in the maximum early diastolic velocity to average early diastolic peak velocity (E/e') ratio (an index of LV diastolic function) via echocardiography.
Of the entire PROCEED trial dataset, 57 participants (ipragliflozin group, n = 28; control group, n = 29) with available echocardiography data at baseline and 24 weeks were included. The primary endpoint was the change in the E/e' ratio from baseline to 24 weeks. The effect of SGLT2 inhibitors on the endpoint was stratified by baseline LVEF, body mass index (BMI), N-terminal pro-brain natriuretic peptide (NT-proBNP) level, estimated glomerular filtration rate (eGFR), and urine albumin-to-creatinine ratio (UACR).
No significant difference in the E/e' ratio changes was observed between the ipragliflozin and control groups (group difference: - 0.82 [95% CI: - 2.44 to 0.81]; P = 0.317). The E/e' ratio was unaffected by baseline NT-proBNP, eGFR, and UACR levels. However, ipragliflozin significantly reduced the E/e' ratio in patients with LVEF ≥ 60% (n = 21, group difference: - 1.42 [- 2.76 to - 0.08]; P = 0.038) or BMI ≥ 25 kg/m (n = 19, group difference: - 1.95 [- 3.56 to - 0.34]; P = 0.020), but not in those with LVEF < 60% (n = 7, group difference: 1.83 [- 4.48 to 8.14]; P = 0.527) or BMI < 25 kg/m (n = 9, group difference: 1.34 [- 1.65 to 4.34]; P = 0.363). Significant interactions were noted between patients with LVEF ≥ 60% and < 60% (P0.048) and BMI ≥ 25 kg/m and < 25 kg/m (P0.016).
In subgroups with higher LVEF and BMI, ipragliflozin improved diastolic function more than standard treatment. These results may partly support the beneficial effect of SGLT2 inhibitors on LV diastolic performance.
钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂对于治疗左心室（LV）射血分数（LVEF）保留的患者很重要。多项研究评估了SGLT2抑制剂对左心室舒张功能的影响，结果相互矛盾。在慢性肾脏病和2型糖尿病中依帕列净治疗内皮功能障碍项目（PROCEED）试验的这项亚分析中——纳入2型糖尿病（T2DM）和慢性肾脏病（CKD）患者——我们通过超声心动图检查了依帕列净与非SGLT2抑制剂标准治疗（对照）相比对舒张早期最大速度与舒张早期平均峰值速度之比（E/e'比值，左心室舒张功能指标）变化的影响。
在整个PROCEED试验数据集中，纳入了57名在基线和24周时有可用超声心动图数据的参与者（依帕列净组，n = 28；对照组，n = 29）。主要终点是从基线到24周E/e'比值的变化。SGLT2抑制剂对终点的影响按基线LVEF、体重指数（BMI）、N末端脑钠肽前体（NT-proBNP）水平、估算肾小球滤过率（eGFR）和尿白蛋白与肌酐比值（UACR）进行分层。
依帕列净组和对照组之间在E/e'比值变化方面未观察到显著差异（组间差异：-0.82 [95%CI：-2.44至0.81]；P = 0.317）。E/e'比值不受基线NT-proBNP、eGFR和UACR水平的影响。然而，依帕列净显著降低了LVEF≥60%患者（n = 21，组间差异：-1.42 [-2.76至-0.08]；P = 0.038）或BMI≥25 kg/m患者（n = 19，组间差异：-1.95 [-3.56至-0.34]；P = 0.020）的E/e'比值，但在LVEF<60%患者（n = 7，组间差异：1.83 [-4.48至8.14]；P = 0.527）或BMI<25 kg/m患者（n = 9，组间差异：1.34 [-1.65至4.34]；P = 0.363）中未降低。在LVEF≥60%与<60%的患者之间（P = 0.048）以及BMI≥25 kg/m与<25 kg/m的患者之间（P = 0.016）观察到显著的交互作用。
在LVEF和BMI较高的亚组中，依帕列净比标准治疗更能改善舒张功能。这些结果可能部分支持SGLT2抑制剂对左心室舒张性能的有益作用。
