Effects of esaxerenone add-on therapy versus angiotensin II receptor blocker dose escalation on albuminuria and blood pressure in hypertensive patients with type 2 diabetes: An exploratory randomized study
In brief
Esaxerenone added to ARB cuts albuminuria about 30% more than dose increase
In a 24-week Japanese trial of 39 hypertensive type-2 diabetics with albuminuria, adding esaxerenone to standard ARB therapy lowered urinary albumin-to-creatinine ratio by roughly 30% compared with simply increasing the ARB dose, and also reduced systolic and diastolic pressures. Kidney filtration fell slightly and oxidative stress was unchanged, leaving safety and long-term benefit to be clarified.
- Journal
- Journal of diabetes investigation (Q1)
- Published
- 5 August 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Makoto Ohara, Takemasa Omachi, Nobuaki Takehana, Tomoki Fujikawa, Naoya Osaka, Shunichiro Irie, et al.
- PMID
- 42555195
- DOI
- 10.1111/jdi.70412
Why clinicians should know about it
- Picked for Internal Medicine (top studies of the week, 9 August 2026): Esaxerenone add‑on reduced albuminuria more than ARB escalation
Abstract
AIMS: Residual albuminuria remains a major clinical challenge in patients with type 2 diabetes mellitus and hypertension despite renin-angiotensin system inhibitor therapy. Esaxerenone, a selective nonsteroidal mineralocorticoid receptor antagonist, reduces albuminuria; however, its effects on oxidative stress remain unclear. MATERIALS AND METHODS: This 24-week, prospective, randomized, open-label, multicenter exploratory trial was conducted in Japan. Hypertensive patients with type 2 diabetes mellitus and albuminuria receiving standard-dose angiotensin II receptor blocker therapy were randomized to angiotensin II receptor blocker dose escalation or esaxerenone add-on therapy. Of 50 randomized patients, 47 were included in the full analysis set and 39 in the final analysis population (20 in the angiotensin II receptor blocker dose-escalation group and 19 in the esaxerenone add-on group). The primary endpoints were changes from baseline to Week 24 in urinary albumin-to-creatinine ratio and oxidative stress assessed by diacron-reactive oxygen metabolites. RESULTS: Esaxerenone add-on therapy produced a significantly greater reduction in log-transformed urinary albumin-to-creatinine ratio than angiotensin II receptor blocker dose-escalation therapy, with an adjusted between-group ratio of 0.71 (95% confidence interval, 0.58-0.87; p = 0.002). Systolic and diastolic blood pressures were significantly lower with esaxerenone. Estimated glomerular filtration rate decreased more with esaxerenone, whereas serum potassium levels did not differ significantly between groups. No significant between-group difference was observed in diacron-reactive oxygen metabolites. CONCLUSIONS: In hypertensive patients with type 2 diabetes mellitus and albuminuria, esaxerenone add-on therapy reduced albuminuria and blood pressure more effectively than angiotensin II receptor blocker dose escalation but did not significantly reduce oxidative stress.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.