CKD & Diabetes: New Therapy Boosts Confidence
In a significant breakthrough, a combination therapy shows promise for patients grappling with CKD and type 2 diabetes. The CONFIDENCE trial revealed that empagliflozin and finerenone significantly reduced albuminuria, offering a beacon of hope for improved kidney health. Results show a 52% reduction in UACR with combo therapy. Moreover, 70% of patients saw substantial improvements. This innovative approach could reshape clinical strategies, as highlighted by the experts in The New England Journal of Medicine, paving the way for better long-term outcomes. News Directory 3 is reporting on these critical findings. Discover what’s next for these innovative treatments.
Combination Therapy Shows Promise in Reducing Albuminuria in CKD and Type 2 Diabetes
Updated June 05, 2025
VIENNA — The CONFIDENCE trial, presented at the 62nd european Renal Association (ERA) congress 2025, revealed that combining the SGLT2 inhibitor empagliflozin with the nonsteroidal mineralocorticoid receptor antagonist (MRA) finerenone significantly and sustainably reduced albuminuria in patients with both chronic kidney disease (CKD) and type 2 diabetes (T2D). The findings, together published in The New England Journal of Medicine, offer hope for improved long-term outcomes for this patient population.
The study demonstrated that 70% of patients receiving both therapies achieved the American Diabetes Association’s recommended urinary albumin-to-creatinine ratio (UACR) reduction target of greater than 30%.
“Since UACR is a key mediator of kidney and cardiovascular outcomes, these results are highly relevant for clinical decision-making,” said lead researcher Dr. Rajiv Agarwal, professor emeritus of medicine at Indiana University School of Medicine.
Dr. Mustafa Arici, professor of medicine (nephrology) at Hacettepe University, described the results as “remarkable,” telling Medscape medical News that the data supports initiating both an SGLT2 inhibitor and an MRA in combination from the outset for type 2 diabetes patients to protect their kidneys.
While Dr. Arici acknowledged the absence of clinical endpoints in the study, he noted the challenges of conducting trials large enough to demonstrate a clinical benefit. He emphasized the significance of the UACR surrogate outcome, the good follow-up duration, and the absence of safety signals in the 800-person study.
Dr. Peter Rossing, clinical professor at Steno Diabetes Center Copenhagen, highlighted the evolving standard of care for patients with CKD and T2D, which now includes SGLT2 inhibitors, MRAs, and GLP-1 receptor agonists alongside ACE inhibitors and arbs. He noted the importance of determining how to best implement and combine these additional drugs.
The CONFIDENCE trial enrolled patients with a UACR between 100 and 5000 mg/g, an estimated glomerular filtration rate (eGFR) of 30-90 mL/min/1.73 m2, T2D with an A1C less than 11%, and who were receiving clinically maximally tolerated doses of ACE inhibitors/ARBs for more than a month. Participants were randomly assigned to receive finerenone plus empagliflozin, finerenone plus placebo, or empagliflozin plus placebo for 180 days.
The primary endpoint was the relative change in UACR from baseline to day 180. The combination therapy achieved a 52% reduction in UACR over baseline, which was 32% greater than empagliflozin alone and 29% greater than finerenone alone.
Furthermore, 70% of patients treated with the combination achieved a greater than 30% reduction in UACR at day 180, compared to 52% of patients treated with either drug alone. The combination therapy also resulted in a 17.7% reduction in the incidence of treatment-emergent hyperkalemia compared to finerenone monotherapy.
Dr. Johannes F.E. Mann, head of the KfH Kidney Center, explained that a recent mediation analysis of pooled data from two phase 3 trials of finerenone revealed that reductions in UACR over the first four months of treatment explained a significant portion of later reductions in kidney progression and cardiovascular outcomes, suggesting that the CONFIDENCE findings may translate into later improvements in clinical endpoints.
Dr. Muthiah Vaduganathan, from Brigham and Women’s Hospital, commented on X that the simultaneous initiation of the combination therapy “safely and rapidly delivers” in patients with both CKD and T2D, signaling “a new age of combination therapies.”
The study was funded by Bayer.
Agarwal declares relationships with Akebia Therapeutics, Alnylam, Bayer Healthcare Pharmaceuticals, Boehringer Ingelheim, Intercept, Novartis, UpToDate, Wolters Kluwer, Chinook, and Vertex.
Rossing declares relationships with AstraZeneca, Bayer, Novo Nordisk, Abbott, Astellas, boehringer Ingelheim, Eli Lilly, Gilead, Sanofi, Daiichi Sankyo, and Lexicon Pharma.
Heerspink declares relationships with Alexion, AstraZeneca, bayer, Boehringer Ingelheim, BioCity, Dimerix, Eli Lilly, Janssen, novartis, Novo Nordisk, Roche, and Travere Therapeutics.
Mann declares relationships with Novo nordisk, the European Union, Bayer, AstraZeneca, Bayer, Novartis, UpToDate, Cytel, IQVIA, Parexel, WCG, and Sanofi.
What’s next
Researchers plan to continue monitoring the patients in the CONFIDENCE trial to assess the long-term impact of the combination therapy on kidney and cardiovascular outcomes. Future studies may also explore the optimal timing and dosing of empagliflozin and finerenone in patients with CKD and T2D.