Combination finerenone and empagliflozin in CKD with diabetes

In people with both chronic kidney disease (CKD) and type 2 diabetes, treatment with finerenone (a non-steroidal mineralocorticoid receptor agonist; nsMRA) and sodium–glucose cotransporter 2 inhibitors (SGLT2i) have independently been demonstrated to be effective in delaying the progression of CKD while improving cardiovascular outcomes. Evidence of the effects of the simultaneous initiation of both drugs, however, has been limited.

Investigators in the CONFIDENCE trial set out to test the hypothesis that the simultaneous use of both agents would decrease urinary albumin-to-creatinine ratio (uACR) more than either treatment alone. Participants were eligible if they had CKD (eGFR of 30–90 mL/min/1.73 m²), albuminuria and type 2 diabetes, and had been receiving an ACE inhibitor or ARB for more than a month. They were randomised in a 1:1:1 ratio to receive finerenone (and empagliflozin-matching placebo) at a dose of 10 or 20 mg/day, empagliflozin at a dose of 10 mg/day (and finerenone-matching placebo) or a combination of the two therapies.

At baseline, mean (±SD) eGFR was 54.2±17.1 mL/min/1.73 m². Across the three treatment groups, uACR was similar with a median value of 579 (IQR, 292–1092) among those with available data (258 in the finerenone group, 261 in the empagliflozin group and 265 in the combination group).

At 180 days after randomisation, the reduction in the uACR with combination therapy was 29% greater than that with finerenone alone (least-squares mean ratio of the difference in the change from baseline, 0.71 [95% CI, 0.61–0.82; P<0.001]) and 32% greater than that with empagliflozin alone (0.68 [0.59–0.79; P<0.001]).

In the combination-therapy group, uACR was reduced by >30% from baseline after 14 days and by >40% after 90 days. Comparing baseline with day 180, the least-squares mean ratio of the change in uACR was 0.48 (0.44–0.54) in the combination-therapy group, 0.68 (0.61–0.76) in the finerenone group and 0.71 (0.64–0.79) in the empagliflozin group. From the end of treatment to the end of follow-up at 210 days, uACR increased but remained below baseline in the combination and finerenone groups.

Serious adverse events occurred in 7.1% of participants in the combination-therapy group, 6.1% in the finerenone group and 6.4% in the empagliflozin group. Events leading to discontinuation were uncommon across all three groups. 

Hyperkalaemia was more common in the combination and finerenone groups (9.3% and 11.4%, respectively) compared to the empagliflozin group (3.8%). However, only one participant in each treatment group discontinued treatment owing to hyperkalaemia. Blood pressure reduction was greatest with combination therapy. The incidence of symptomatic hypotension was low.

Among people with both CKD and type 2 diabetes, the reduction by 52% in uACR in those undergoing combination therapy suggests that the effects of finerenone and empagliflozin are additive, and more effective than either drug alone. 

The full article can be read here.