Empagliflozin 25 mg confers greater kidney protection than SGLT2i 10 mg in T2D

In patients with type 2 diabetes (T2D), empagliflozin 25 mg daily offers greater kidney protection than its 10 mg daily dose or dapagliflozin 10 mg daily, a retrospective cohort study in Hong Kong has shown.

Researchers from the Chinese University of Hong Kong and the Hospital Authority’s New Territories East Cluster analyzed data from patients with T2D and no history of end-stage kidney disease (ESKD) who were enrolled in the Hong Kong Diabetes Surveillance Database (HKDSD) Risk Assessment and Management Programme for Diabetes Mellitus (RAMP-DM) in 2000–2019 and started on sodium-glucose cotransporter 2 inhibitors (SGLT2i). [Cheung JTK, et al, EmW 2025]

A total of 20,259 patients (mean age, 59.5 years; male, 57.6 percent; mean T2D duration, 13.9 years; mean HbA_1c, 8.7 percent; mean BMI, 28.0 kg/m²) were included in the 1:1:1 propensity score–matched cohort to compare kidney outcomes between dapagliflozin 10 mg (n=6,753), empagliflozin 10 mg (n=6,753), and empagliflozin 25 mg (n=6,753).

At baseline, 25.3 percent of the cohort had cardiovascular (CV) disease, 4.6 percent had heart failure (HF), and 2.7 percent had chronic kidney disease. Mean urine albumin-to-creatinine ratio was 16.6 mg/mmol, while mean estimated glomerular filtration rate (eGFR) was 84.5 mL/min/1.73 m². Kidney Disease Improving Global Outcomes (KDIGO) risk was low in 51.5 percent of patients, moderately increased in 32.6 percent, and high or very high in 15.9 percent.

Baseline medications were predominantly metformin (94.6 percent) and renin-angiotensin system inhibitors (69.7 percent), followed by sulfonylureas (60.6 percent) and dipeptidyl peptidase-4 inhibitors (52.9 percent).

Potential dose-response relationship in kidney protection

Over a median follow-up of 17.8 months, mean annual eGFR decline after SGLT2i initiation was slowest in the empagliflozin 25 mg group (-1.35 mL/min/1.73 m²/year; fixed-effect p<0.001). Mean eGFR slopes were comparable between the empagliflozin 10 mg and dapagliflozin 10 mg groups (-1.89 vs -1.77 mL/min/1.73 m²/year; fixed-effect p=0.312). Findings were generally consistent across subgroups.

The risk of the kidney composite endpoint of sustained eGFR decline >40 percent (two consecutive measurements), ESKD, CV or renal mortality, or hospitalization was significantly lower with empagliflozin 25 mg vs 10 mg (hazard ratio [HR], 0.62; 95 percent confidence interval [CI], 0.52–0.73; p<0.0001), and comparable between dapagliflozin 10 mg and empagliflozin 10 mg (HR, 0.98; 95 percent CI, 0.84–1.15).

Acute kidney injury during hospitalization episodes was significantly reduced with empagliflozin 25 mg vs 10 mg (HR, 0.43; 95 percent CI, 0.27–0.69; p=0.0012), and not significantly different between dapagliflozin 10 mg and empagliflozin 10 mg (HR, 0.89; 95 percent CI, 0.60–1.32).

Sustained eGFR decline >40 percent and all-cause mortality were significantly reduced with empagliflozin 25 mg vs 10 mg (HR, 0.62 [95 percent CI, 0.52–0.73; p<0.0001] and 0.43 [95 percent CI, 0.33–0.58; p<0.0001], respectively), and not significantly different between dapagliflozin 10 mg and empagliflozin 10 mg.

“Empagliflozin 25 mg may confer greater kidney protection than empagliflozin 10 mg and dapagliflozin 10 mg, suggesting a potential dose-response relationship,” the researchers concluded.

“Further studies should include randomized controlled trials and economic evaluation to assess comparative effectiveness and cost-effectiveness, and mediation analysis to explore mechanisms such as HbA_1c reduction and haemoglobin improvement,” they added.