Bayer announced results from the Phase II CONFIDENCE study demonstrating that simultaneous initiation of finerenone (Kerendia™) and the SGLT-2 inhibitor empagliflozin led to significantly greater reduction in urine albumin-to-creatinine ratio (UACR) in adults with chronic kidney disease (CKD) associated with type 2 diabetes than either treatment alone. The findings were presented at the 62nd European Renal Association (ERA) Congress 2025 and simultaneously published in the New England Journal of Medicine.
Superior Efficacy with Combination Therapy
The CONFIDENCE study showed that simultaneous initiation with finerenone and empagliflozin in patients with CKD associated with type 2 diabetes led to an early and additive reduction in UACR from baseline of 52% at Day 180. This represented a 29% and 32% greater relative reduction in UACR from baseline to Day 180 compared to finerenone alone and empagliflozin alone, respectively.
Notably, a reduction of more than 30% in UACR was observed within 14 days of starting both treatments simultaneously – a threshold recommended by the American Diabetes Association (ADA) to slow kidney disease progression in patients with CKD. Almost three out of four patients achieved this threshold of a 30% reduction in UACR versus baseline – 20% more than with either treatment alone.
"The CONFIDENCE study delivers clinical evidence that simultaneous initiation of finerenone and empagliflozin led to an early and additive reduction in UACR of 52% in patients with chronic kidney disease and type 2 diabetes, which was significantly greater than with either treatment alone," said Rajiv Agarwal, MD, Professor Emeritus of Medicine, Indiana University School of Medicine and VA Medical Centre, Indianapolis, USA and Chair of the study's Steering Committee.
Clinical Significance and Safety Profile
The safety profile of simultaneous initiation of finerenone and SGLT-2 inhibitor was consistent with that of either agent alone, and treatment benefits were seen across all prespecified subgroups enrolled in the study, across a broad spectrum of patient populations with a high comorbidity burden.
Safety analyses suggested there were no unexpected adverse events with either agent alone or in combination. Less than 5% of patients experienced adverse events leading to discontinuation. Serious adverse events were observed in 7.1% of the combination therapy group, 6.1% of the finerenone group, and 6.4% of the empagliflozin group. One participant from each study group discontinued the trial due to hyperkalemia.
Study Design and Patient Population
The CONFIDENCE study was a randomized, double-blind, double-dummy, multicenter, three-arm, parallel-group treatment, Phase II study. The primary objective was to determine whether the simultaneous initiation and combined use of finerenone and empagliflozin would be superior to either treatment alone in reducing UACR in patients with CKD and type 2 diabetes.
The study randomized 818 patients in a 1:1:1 ratio, stratified by estimated glomerular filtration rate (eGFR) and UACR at screening. Patients received either finerenone (10 or 20 mg once daily) and empagliflozin (10 mg), finerenone (10 or 20 mg) and matching placebo, or empagliflozin (10 mg) and matching placebo.
For inclusion in the trial, patients were required to have type 2 diabetes with HbA1c levels less than 11%, an eGFR between 30 and 90 ml/min/1.73m² of body surface area, and albuminuria, defined as a UACR between 100 and 5000 mg.
Addressing Unmet Medical Need
Diabetes continues to be a substantial public health issue, with an estimated 462 million people globally affected by type 2 diabetes alone. Approximately 40% of people with type 2 diabetes go on to develop CKD, highlighting a significant unmet medical need for therapies that can better protect kidney function and slow disease progression.
"The CONFIDENCE data mark an important milestone in our mission to improve care for people living with chronic kidney disease associated with type 2 diabetes," said Dr. Michael Devoy, Chief Medical Officer at Bayer's Pharmaceuticals Division. "The findings suggest that a proactive simultaneous initiation can deliver a substantial early and additive UACR reduction, which is associated with kidney and cardiovascular protection."
Clinical Context and Future Implications
Finerenone, a non-steroidal, selective mineralocorticoid receptor (MR) antagonist, has been investigated in a broad patient population with CKD (stages 1-4) associated with type 2 diabetes across two completed and published Phase III studies, FIDELIO-DKD and FIGARO-DKD. Data from FIDELITY, a prespecified pooled analysis of these Phase III studies, confirm that early albuminuria (UACR) reduction in patients with CKD associated with type 2 diabetes mediated a large proportion of the treatment effect of finerenone in slowing CKD progression.
The new era of combination therapy in CKD in type 2 diabetes, often referred to as a pillared approach, has evolved significantly in the last decade. The field now has four foundational classes of therapy with proven benefits: RAASi, SGLT2 inhibitors, GLP-1 receptor agonists, and nonsteroidal mineralocorticoid receptor agonists.
