Kuwabara Saki, Kameda Hiraku, Yokozeki Kei, Miya Aika, Nomoto Hiroshi, Cho Kyu Yong, Nakamura Akinobu, Koyanagawa Naohide, Yamamoto Kohei, Takeuchi Jun, Nagai So, Miyoshi Arina, Wada Norio, Taneda Shinji, Kurihara Yoshio, Atsumi Tatsuya
Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Division of Endocrinology, Metabolism, and Rheumatology, Department of Internal Medicine, Asahikawa Medical University, Asahikawa, Japan.
Endocr J. 2025 Aug 1;72(8):947-957. doi: 10.1507/endocrj.EJ24-0639. Epub 2025 May 30.
Esaxerenone, a nonsteroidal mineralocorticoid receptor blocker, may be an effective treatment for diabetes-associated mineralocorticoid receptor-related hypertension, but there have been few studies of its use in clinical practice. We aimed to determine the effects of esaxerenone on blood pressure (BP) and metabolic parameters of hypertensive subjects with diabetes in a clinical practice setting. We performed a retrospective multicenter observational study of hypertensive subjects with type 2 diabetes/prediabetes. We first compared the values of parameters at baseline and after 6 months of esaxerenone administration, then compared the changes in the parameters in propensity score-matched subjects who initiated esaxerenone or amlodipine administration. Correlation analysis was performed to identify factors associated with these changes. The single-arm analysis showed that esaxerenone caused significant reductions in systolic and diastolic BP from 155.2 ± 17.7 and 83.3 ± 12.3 mmHg at baseline to 132.9 ± 15.5 and 72.3 ± 12.9 mmHg, respectively, after 6 months of treatment (p < 0.01). In addition, body mass index (BMI), glycated hemoglobin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol, low-density lipoprotein-cholesterol, estimated glomerular filtration rate, and urine albumin/creatinine ratio (UACR) significantly decreased (p < 0.05). The esaxerenone group showed significantly larger reductions in systolic BP, AST, ALT, and UACR than the amlodipine group (p < 0.05). Furthermore, there was a negative correlation between the change in ALT and baseline BMI (p < 0.05). Esaxerenone has an antihypertensive effect, reduces the albuminuria, and reduces the activities of liver enzymes in hypertensive subjects with type 2 diabetes/prediabetes. The present findings suggest that esaxerenone has pleiotropic effects in such subjects.
依普利酮是一种非甾体类盐皮质激素受体阻滞剂，可能是治疗糖尿病相关盐皮质激素受体相关高血压的有效药物，但在临床实践中对其应用的研究较少。我们旨在确定依普利酮在临床实践中对糖尿病高血压患者血压（BP）和代谢参数的影响。我们对2型糖尿病/糖尿病前期高血压患者进行了一项回顾性多中心观察性研究。我们首先比较了依普利酮给药6个月时基线和之后的参数值，然后比较了开始使用依普利酮或氨氯地平给药的倾向评分匹配受试者参数的变化。进行相关性分析以确定与这些变化相关的因素。单臂分析显示，依普利酮治疗6个月后，收缩压和舒张压从基线时的155.2±17.7和83.3±12.3 mmHg分别显著降低至132.9±15.5和72.3±12.9 mmHg（p<0.01）。此外，体重指数（BMI）、糖化血红蛋白、天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、总胆固醇、低密度脂蛋白胆固醇、估算肾小球滤过率和尿白蛋白/肌酐比值（UACR）显著降低（p<0.05）。依普利酮组的收缩压、AST、ALT和UACR降低幅度明显大于氨氯地平组（p<0.05）。此外，ALT变化与基线BMI之间存在负相关（p<0.05）。依普利酮具有降压作用，可减少蛋白尿，并降低2型糖尿病/糖尿病前期高血压患者的肝酶活性。目前的研究结果表明，依普利酮在此类患者中具有多效性作用。
