What is the clinical evidence from this study?

Study design: RCT. Population: Uncontrolled essential hypertension with type 2 diabetes mellitus (n=234). Intervention: Esaxerenone vs. Trichlormethiazide. Primary outcome: Change in morning home systolic blood pressure from baseline to end of treatment (Mean Difference -2.5, 95% CI -4.8, -0.2).

What does this research mean for the field?

Esaxerenone is non-inferior to trichlormethiazide and superior for reducing morning home systolic blood pressure in hypertensive patients with type 2 diabetes, while maintaining a favorable safety profile and reducing kidney damage. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

December 23, 2025Hypertension Research1 citationsOpen Access

Efficacy and safety of esaxerenone vs trichlormethiazide for the treatment of uncontrolled essential hypertension in Japanese patients with type 2 diabetes mellitus: a subanalysis of the EXCITE-HT study

MOMitsuru OhishiKagoshima University KKKazuomi KarioJichi Medical University TKTomohiro KatsuyaOsaka Gakuin University

Key Result

Esaxerenone was non-inferior to trichlormethiazide and superior for reducing morning home systolic blood pressure (mean difference -2.5 mmHg) in hypertensive patients with type 2 diabetes.

Study Design

Type

RCT (n=234)

Blinding

Open-label

Randomization

Randomized

Multicenter

Yes

Structured PICO

Does esaxerenone reduce morning home SBP/DBP compared to trichlormethiazide in Japanese patients with type 2 diabetes mellitus and uncontrolled essential hypertension?

Population

n=234 Japanese adults with type 2 diabetes mellitus and uncontrolled essential hypertension (mean morning home SBP ≥125 mmHg and/or DBP ≥75 mmHg) on background ARB or CCB therapy for ≥4 weeks. Mean age 66.4 (esaxerenone) and 66.0 (trichlormethiazide), ~58% male.

Intervention

Esaxerenone 1.25 to 5 mg oral once daily added to baseline ARB or CCB for 12 weeks.

Comparator

Trichlormethiazide ≤1 mg to 2 mg oral once daily added to baseline ARB or CCB for 12 weeks.

Outcome

Change in morning home SBP/DBP from baseline to end of treatment (12 weeks).surrogate

Main Result

Effect estimate: Mean Difference -2.5 (95% CI -4.8, -0.2)

Absolute Event Rate: -12.1% vs -9.6%

Limitations

Exploratory nature of the subgroup analysis
Relatively short follow-up period of 12 weeks
Small sample size
Baseline antihypertensive agents prescribed at physicians' discretion, which may have introduced bias
Possible inclusion of patients with primary aldosteronism

Abstract

This subgroup analysis of the randomized, open-label, parallel-group EXCITE-HT study explored the antihypertensive efficacy and safety of esaxerenone vs trichlormethiazide in patients with type 2 diabetes mellitus (T2DM), stratified by baseline antihypertensive agent (angiotensin receptor blocker ARB or calcium channel blocker CCB) and urinary albumin-to-creatinine ratio (UACR; <30 or ≥30 mg/gCr). Using thresholds consistent with those used in the main study to interpret the difference in systolic/diastolic blood pressure (SBP/DBP), the between-group difference in least squares mean change (95% confidence interval CI) in morning home SBP/DBP at the end of treatment was -2.5 (-4.8, -0.2)/ - 0.7 (-2.0, 0.6) mmHg. Trends were consistent across all subgroups. The geometric mean UACR significantly decreased from baseline to Week 12 in the overall population, ARB subgroup (except for esaxerenone-treated patients), CCB subgroup, and both UACR subgroups. The overall incidence of serum potassium ≥5.5 mEq/L was 2.5% with esaxerenone and 0.9% with trichlormethiazide, with no cases of serum potassium ≥6.0 mEq/L. In this patient population, esaxerenone had a favorable safety profile, achieved blood pressure lowering similar to trichlormethiazide, and elicited a reduction of kidney damage (based on UACR), regardless of baseline antihypertensive agent or UACR.

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