Finerenone and Empagliflozin Combo Significantly Reduces Albuminuria in CKD with T2D: new data from CONFIDENCE Trial

New findings from the CONFIDENCE trial show that combination therapy with finerenone and empagliflozin leads to significantly greater reductions in albuminuria compared to either drug alone in patients with chronic kidney disease and type 2 diabetes. Results were presented at the 62nd ERA Congress and published in the New England Journal of Medicine.

For many patients, albuminuria is the earliest sign of CKD.2 Increased levels of albuminuria is linked to a faster rate of CKD progression in both diabetic and nondiabetic kidney disease patients.

Finerenone, a selective nonsteroidal mineralocorticoid receptor antagonist (nsMRA), and SGLT2 inhibitors like empagliflozin have independently demonstrated efficacy in delaying CKD progression and improving cardiovascular outcomes. The CONFIDENCE study is the first randomised trial to test the hypothesis that early, simultaneous use of both agents would provide superior reduction in urinary albumin-to-creatinine ratio (UACR) over 6 months, compared to either drug alone.

This phase 2, multicentre, randomised, double-blind trial enrolled 818 adults with CKD (eGFR 30–90 ml/min/1.73 m²) and T2D, with a UACR between 100 and <5,000 mg/g, all receiving a maximally tolerated dose of a renin–angiotensin system inhibitor for at least one month. Participants were randomised in a 1:1:1 ratio to receive empagliflozin 10 mg once daily + placebo, finerenone 10 or 20 mg once daily + placebo, or a combination of finerenone and empagliflozin, with doses adjusted based on baseline eGFR. Baseline clinical characteristics were published in Nephrology Dialysis Transplantation on 7 February 2025.

Randomisation was stratified by eGFR (< or ≥60 ml/min/1.73 m²) and UACR (≤ or >850 mg/g). Patients were recruited from 143 sites across 14 countries between July 2022 and August 2024, ensuring a diverse population with a high burden of comorbidities, including cardiovascular disease (28%), diabetic retinopathy (16%), and heart failure (4%).

At Day 180, the combination group showed a 52% median reduction in UACR from baseline, which was significantly greater than reductions seen with either drug alone. Specifically, UACR was reduced by an additional 29% compared to finerenone alone (P<0.001) and by 32% compared to empagliflozin alone (P<0.001).

“The CONFIDENCE study delivers the clear message that simultaneous initiation of finerenone and empagliflozin led to an early and additive reduction in UACR of 52% in patients with CKD and T2D, which was significantly greater than with either treatment alone,” said lead researcher Dr. Rajiv Agarwal.

“In other chronic conditions like heart failure or hypertension, we’re moving away from the traditional stepwise approach toward upfront combination therapy,” Dr. Agarwal explained. “In CONFIDENCE, 70% of patients on both therapies achieved the ADA-recommended UACR reduction target of >30%. Since UACR is a key mediator of kidney and cardiovascular outcomes, these results are highly relevant for clinical decision-making.”

Importantly, combination therapy was well tolerated, with no unexpected safety signals. Rates of symptomatic hypotension, acute kidney injury, and hyperkalemia leading to treatment discontinuation were low.

The findings support a paradigm shift toward early, dual-pathway intervention in CKD and T2D, offering clinicians a new, evidence-based strategy to optimise outcomes in a population at high risk of kidney and cardiovascular complications.

Reference:

Combination finerenone and empagliflozin shows superior efficacy in reducing albuminuria in chronic kidney disease and type 2 diabetes patients, Beyond, Meeting: 62nd ERA Congress.