Background

Empagliflozin slowed the progression of CKD in patients with type 2 diabetes and cardiovascular disease in the EMPA-REG OUTCOME Trial. In a prespecified statistical approach, we assessed treatment differences in kidney function by analyzing slopes of eGFR changes.

Methods

Participants (n=7020) were randomized (1:1:1) to empagliflozin 10 mg/d, empagliflozin 25 mg/d, or placebo added to standard of care. We calculated eGFR slopes using random-intercept/random-coefficient models for prespecified study periods: treatment initiation (baseline to week 4), chronic maintenance treatment (week 4 to last value on treatment), and post-treatment (last value on treatment to follow-up).

Results

Compared with placebo, empagliflozin was associated with uniform shifts in individual eGFR slopes across all periods. On treatment initiation, adjusted mean slope (eGFR change per week, ml/min per 1.73 m²) decreased with empagliflozin (–0.77; 95% confidence interval, –0.83 to –0.71; placebo: 0.01; 95% confidence interval, –0.08 to 0.10; P<0.001). However, annual mean slope (ml/min per 1.73 m² per year) did not decline with empagliflozin during chronic treatment (empagliflozin: 0.23; 95% confidence interval, 0.05 to 0.40; placebo: –1.46; 95% confidence interval, –1.74 to –1.17; P<0.001). After drug cessation, the adjusted mean eGFR slope (ml/min per 1.73 m² per week) increased and mean eGFR returned toward baseline level only in the empagliflozin group (0.56; 95% confidence interval, 0.49 to 0.62; placebo –0.02; 95% confidence interval, –0.12 to 0.08; P<0.001). Results were consistent across patient subgroups at higher CKD risk.

Conclusions

The hemodynamic effects of empagliflozin, associated with reduction in intraglomerular pressure, may contribute to long-term preservation of kidney function.