Impact of Simultaneous Initiation of Finerenone and Empagliflozin on Urinary Albumin-to-Creatinine Ratio in Asia

Key Points Finerenone plus empagliflozin was more effective in reducing urinary albumin-to-creatinine ratio than either drug alone in Asian participants of the CONFIDENCE trial. Except for hyperkalemia, adverse events and serious adverse events were less frequent in participants from Asia than in the overall CONFIDENCE trial population. The risk–benefit profile of the combination seems similarly favorable in people from Asia as in the overall CONFIDENCE trial population. Background The COmbinatioN effect of FInerenone anD EmpaglifloziN in participants with CKD and type 2 diabetes using a urinary albumin-to-creatinine ratio (UACR) Endpoint (CONFIDENCE) trial compared simultaneous initiation of finerenone with empagliflozin versus either drug alone. We report a pre-specified participant-level exploratory analysis of outcomes in the subpopulation from Asia (India, Japan, the Republic of Korea, and Taiwan). Methods Adults with CKD and type 2 diabetes with UACR between 100 and 5000 mg/g and on a renin–angiotensin system inhibitor were recruited. Participants were randomized 1:1:1 to 180 days of treatment with finerenone 10/20 mg once daily (and empagliflozin-matching placebo), empagliflozin 10 mg once daily (and finerenone-matching placebo), or a combination of both. The primary efficacy outcome was change from baseline in UACR at 180 days. Safety and tolerability were also assessed. Results This analysis included 360 participants from Asia. At day 180, the reduction in UACR with combination therapy was 30% greater than that with finerenone alone (95% confidence interval [CI], 12% to 45%; P = 0.003) and 34% greater than that with empagliflozin alone (95% CI, 16% to 47%; P < 0.001). In general, adverse and serious adverse events were numerically less common in participants from Asia than in those from Europe/North America, except for hyperkalemia. Investigator-reported (10% versus 7%) and laboratory-assessed hyperkalemia (serum potassium >5.5 mmol/L; 19% versus 11%) were more frequent in participants from Asia; however, eGFR declines of >30% at day 30 were less frequent in Asia (3% versus 5%). Conclusions Simultaneous initiation of finerenone and empagliflozin was effective and well tolerated among CONFIDENCE study participants from Asia, consistent with the overall population.