Motoki Hirohiko, Kuwahara Koichiro, Uchida Haruhito A, Wada Jun, Kario Kazuomi, Katsuya Tomohiro, Shimosawa Tatsuo, Tsujita Kenichi, Suzuki Shoko, Suedomi Tomohiro, Taguchi Takashi
Department of Cardiovascular Medicine, Shinshu University School of Medicine, Nagano, Japan.
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Hypertens Res. 2025 Sep 1. doi: 10.1038/s41440-025-02347-0.
This pooled subanalysis of five multicenter, prospective, open-label, single-arm studies on esaxerenone aimed to evaluate the efficacy, organ-protective effects, and safety of esaxerenone in hypertensive patients with type 2 diabetes mellitus (T2DM), with and without concomitant sodium-glucose cotransporter-2 inhibitor (SGLT2i) therapy. In total, 283 and 279 patients were included in the safety (with SGLT2i, 148; without, 135) and full analysis sets (with SGLT2i; 145; without, 134), respectively. Significant changes in morning home systolic/diastolic blood pressure (SBP/DBP) from baseline to Week 12 were shown in the overall population (mean change: -11.9/-5.2 mmHg, both P < 0.001) and both SGLT2i and non-SGLT2i subgroups (-11.3/-4.8 and -12.5/-5.7 mmHg, respectively, all P < 0.001). Similar findings were observed in bedtime home and office SBP/DBP. The proportions of patients who achieved target home SBP/DBP < 135/85 mmHg were 71.2% (overall population) and 70.5% and 71.9% in the SGLT2i and non-SGLT2i subgroups, respectively. The urine albumin-to-creatinine ratio significantly improved from baseline to Week 12 in the overall population and SGLT2i subgroups (percentage change in geometric mean from baseline: -42.8%, -43.0%, and -42.6%, respectively, all P < 0.001). N-terminal pro-B-type natriuretic peptide levels improved in all groups. The incidence of serum potassium ≥5.5 mEq/L was 2.0% vs 5.2% in the SGLT2i vs non-SGLT2i subgroups. Esaxerenone demonstrated significant BP-lowering effects, and improved renal and cardiovascular parameters, regardless of SGLT2i use. Safety was consistent across groups, with the numerically lower incidence of serum potassium ≥5.5 mEq/L in the SGLT2i subgroup suggesting a potential mitigating effect of SGLT2is on the risk of hyperkalemia.
这项对五项关于依沙库利酮的多中心、前瞻性、开放标签、单臂研究的汇总亚组分析旨在评估依沙库利酮在伴有或不伴有钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）治疗的2型糖尿病（T2DM）高血压患者中的疗效、器官保护作用和安全性。安全性分析集（使用SGLT2i的患者有148例，未使用的有135例）和完整分析集（使用SGLT2i的患者有145例，未使用的有134例）分别纳入了283例和279例患者。从基线到第12周，总体人群的清晨家庭收缩压/舒张压（SBP/DBP）有显著变化（平均变化：-11.9/-5.２mmHg，P均<0.001），SGLT2i亚组和非SGLT2i亚组也有类似变化（分别为-11.3/-4.8和-12.5/-5.7mmHg，P均<0.001）。就寝时家庭和办公室的SBP/DBP也有类似发现。达到家庭目标SBP/DBP<135/85mmHg的患者比例在总体人群中为71.2%，在SGLT2i亚组和非SGLT2i亚组中分别为70.5%和71.9%。从基线到第12周，总体人群和SGLT2i亚组的尿白蛋白与肌酐比值均显著改善（几何平均数相对于基线的百分比变化分别为-42.8%、-43.0%和-42.6%，P均<0.001）。所有组的N末端B型利钠肽前体水平均有所改善。SGLT2i亚组和非SGLT2i亚组血清钾≥5.5mEq/L的发生率分别为2.0%和5.2%。无论是否使用SGLT2i，依沙库利酮均显示出显著的降压作用，并改善了肾脏和心血管参数。各亚组安全性一致，SGLT2i亚组血清钾≥5.5mEq/L的发生率在数值上较低，提示SGLT2i对高钾血症风险可能有减轻作用。
