Effect of dapagliflozin-spironolactone combination therapy versus monotherapy on albuminuria reduction and hyperkalemia risk in elderly patients with early type 2 diabetic nephropathy receiving high-dose RASi: A randomized controlled trial.

BACKGROUND

This randomized controlled trial evaluated the efficacy and safety of dapagliflozin-spironolactone combination therapy versus monotherapy in reducing urinary albumin excretion rate (UAER) and mitigating hyperkalemia risk in elderly patients with early type 2 diabetic nephropathy (DN) receiving high-dose renin-angiotensin system inhibitors (RASi).

METHODS

In this prospective, open-label, parallel-group study, 168 elderly patients with early DN and mild-to-moderate hypertension were randomized to Group A (irbesartan 300 mg/d plus dapagliflozin 10 mg/d), Group B (irbesartan 300 mg/d plus spironolactone 20 mg/d), or Group C (irbesartan plus dapagliflozin and spironolactone). The primary endpoint was the change in UAER from baseline to week 72. Secondary outcomes included changes in blood pressure, serum potassium levels, and safety profiles.

RESULTS

Baseline characteristics were well-balanced (P > 0.05). Blood pressure remained comparable across groups during follow-up (P > 0.05). After 72 weeks, intention-to-treat analysis showed that Group C achieved a significantly greater UAER reduction compared to Group A and Group B (P < 0.05). Additionally, Group B exhibited higher serum potassium levels than Group A and Group C (P < 0.05), leading to a higher discontinuation rate due to hyperkalemia (P < 0.05).

CONCLUSIONS

In elderly patients with early DN on high-dose RASi, dapagliflozin-spironolactone combination therapy achieved superior albuminuria reduction compared with either monotherapy, while attenuating the risk of spironolactone-associated hyperkalemia. Although no case of hyperkalemia occurred in the combination group in our trial, serum potassium was notably elevated relative to dapagliflozin monotherapy, underscoring the importance of regular monitoring in this population.