December 24, 2025
3 min read
Key takeaways:
- Adults with type 2 diabetes and CKD had a greater UACR reduction with finerenone plus empagliflozin vs. either drug alone.
- Incidence of hyperkalemia and acute kidney injury were low in all groups.
Combination therapy with a nonsteroidal mineralocorticoid receptor antagonist and an SGLT2 inhibitor reduced albuminuria more than monotherapy among adults with type 2 diabetes and chronic kidney disease, according to a speaker.
As Healio previously reported ,in the CONFIDENCE trial, adults with type 2 diabetes and CKD who received once-daily finerenone (Kerendia, Bayer) plus once-daily empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) had a greater reduction in urinary albumin-to-creatine ratio (UACR) at 180 days than those receiving either medication on its own. During a talk at the World Congress on Insulin Resistance, Diabetes and Cardiovascular Disease, Jennifer B. Green, MD, professor of medicine in the division of endocrinology at Duke Clinical Research Institute and Duke University School of Medicine, discussed how starting two different medication classes at the same time could confer greater reductions in albuminuria than monotherapy.
Combination therapy with finerenone plus an SGLT2 inhibitor conferred greater reductions in albuminuria than monotherapy. Image: Adobe Stock
“In part, the rationale for the design and conduct of the CONFIDENCE trial was to try to mimic the approach that has been taken in the implementation of combinations of therapies for condition such as hypertension, where it’s clear that starting two drugs at once, for example, results in better adherence, more rapid and effective achievement of goals or targets for the particular individual, and offers the potential for better tolerability,” Green said during a presentation.
Trial results
In the CONFIDENCE trial, researchers enrolled 800 adults with type 2 diabetes and CKD with an estimated glomerular filtration rate of 30 mL/min/1.73 m2 to 90 mL/min/1.73 m2 and a UACR of 1,000 mg/g to 5,000 mg/g who had previously taken the maximally tolerated dose of ACE inhibitors or angiotensin receptor blockers for more than 1 month. Participants were randomly assigned, 1:1:1, to receive once-daily 10 mg or 20 mg finerenone and once-daily 10 mg empagliflozin (n = 269), once-daily 10 mg or 20 mg finerenone plus placebo (n = 264), or once-daily 10 mg empagliflozin plus placebo (n = 267). The primary efficacy endpoint was change in UACR with finerenone plus empagliflozin compared with each drug alone.
Adults receiving combination finerenone and empagliflozin had a 32% greater decline in UACR compared with the empagliflozin group and a 29% greater reduction than the finerenone group at 180 days. UACR decreased by 52% from baseline to 180 days for those receiving combination therapy.
Of the participants, 70% in the combination therapy group achieved a UACR decrease of at least 30% at 180 days vs. 52% in each of the finerenone and empagliflozin monotherapy groups. A significant UACR reduction was observed for all adults receiving combination therapy, regardless of CKD risk.
Safety data
Adults receiving combination therapy had a rise in potassium ion levels 14 days after starting treatment, though Green said levels returned to baseline 30 days after therapy ended. Green added that potassium ion levels were lower at baseline in the combination group compared with the finerenone and empagliflozin groups, and incidence of treatment-emergent hyperkalemia was 18.4% lower with combination therapy vs. finerenone alone.
“Treatment-emergent hyperkalemia is bound to occur irrespective of what treatment you are on,” Green said. “Fortunately, there were very few events of treatment-emergent hyperkalemia that required permanent discontinuation of the study drug.”
Symptomatic hypotension occurred in 1.1% of the combination therapy group and in none of the participants receiving either study drug alone. Acute kidney injury was reported in 1.9% of adults receiving combination therapy, 1.1% of those receiving finerenone and no participants receiving empagliflozin.
“The safety of [a combination therapy] approach appeared justified based on the results,” Green said.
Green said similar findings to the CONFIDENCE trial were also reported with another combination therapy. In findings from a phase 2b trial published in The Lancet in November, adults with CKD and albuminuria receiving 15 mg or 40 mg of the nonsteroidal mineralocorticoid receptor antagonist balcinrenone (AstraZeneca) plus 10 mg of the SGLT2 inhibitor dapagliflozin (Farxiga, AstraZeneca) had greater decreases in UACR than those receiving dapagliflozin 10 mg plus placebo.
Sources/Disclosures
Source:
Green JB. Session 2 – Insulin resistance – comorbidities. Presented at: World Congress on Insulin Resistance, Diabetes and Cardiovascular Disease; December 3-6, 2025; Los Angeles.
References:
Disclosures:
Green reports receiving research support from Bluedrop, Boehringer Ingelheim, COUR, Eli Lilly, GentiBio, Merck and Roche; and consulting for AstraZeneca, Bayer, Boehringer Ingelheim, Corcept, Eli Lilly, Merck, Mineralys, Novo Nordisk, Valo, Vertex and Zealand.
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