New Data From the CONFIDENCE Trial: The Effect of Combination Empagliflozin and Finerenone on UACR and eGFR in CKD and Type 2 Diabetes

Announcer:
Welcome to DataPulse from ASN Kidney Week 2025 on ReachMD. This activity, titled “New Data From the CONFIDENCE Trial: The Effect of Combination Empagliflozin  and Finerenone on UACR  and eGFR in Chronic Kidney Disease and Type 2 Diabetes” is provided by Medcon International.

Dr. Heerspink:
Hello, everyone. This is Hiddo Heerspink from the University of Groningen here at ASN Kidney Week 2025 in Houston. I'll be reviewing data from the CONFIDENCE trial, and we present new data from the CONFIDENCE trial here at the ASN.

The CONFIDENCE trial was a double-blind, randomized, active-controlled clinical trial in 800 participants with diabetic kidney disease. These participants were receiving RAS inhibition. The albuminuria was between 100 and 5,000 mg/g, and these participants had a GFR between 30 and 90. Eligible participants were randomized 1:1:1 to finerenone, empagliflozin, or their combination.

The primary results of the trial were presented 6 months ago at the European Renal Association meeting in Vienna, and those results showed that combination treatment with finerenone and empagliflozin reduced albuminuria after 6 months by 52%. The combination reduced albuminuria more than finerenone alone—a 29% greater reduction—and more than empagliflozin alone—a 32% greater reduction.

Since the presentation of the CONFIDENCE trial, we already have published multiple manuscripts in journals looking, for example, at the effect of empagliflozin and finerenone on top of GLP-1 agonists. We have looked at the effect specifically in people from Asia. And here at the ASN, we present new data on hyperkalemia.

But the topic for today is that I want to discuss with you the eGFR dip that we observed in the CONFIDENCE trial, because combination treatment with empagliflozin and finerenone caused an acute dip in GFR of about 5 to 6 mL/min. That was more than finerenone or empagliflozin alone. This had led to some concerns by physicians whether they should continue the medication or whether they should discontinue the medication, because some physicians believe that this dip may actually reflect a structural worsening of kidney function.

We believe it's the opposite—both finerenone and empagliflozin reduce the intraglomerular pressure in the kidney, because this is how these drugs work. They reduce the pressure in the kidney, thereby they reduce the hyperfiltration in the kidney. And we know that it is, in the long term, associated with kidney protection.

Importantly, when we discontinued the medication in the CONFIDENCE trial after the 6 months of treatment, we saw that the acute dip in eGFR was completely reversible. So patients in whom the eGFR fell by 5 mL/min had an increase directly after stopping the medication of 5 mL/min. And this suggests that this acute dip in GFR is not a structural worsening of kidney function—it is a so-called hemodynamic effect.

In the last couple of months, we have done additional analyses to assess whether this reversibility in eGFR after discontinuation is consistent in different patient subgroups, and it is. It is consistent in old and young people, males and females, those with or without cardiovascular disease, those with high or low albuminuria.

What is the clinical consequence of this finding? I believe that as a physician, you don't have to be concerned when you see an acute dip in GFR when you initiate combined treatment with finerenone and empagliflozin. This means that you don't have to down-titrate a dose or you don't have to discontinue the medication. It means that the patient is adherent to the medication and that you can continue the medication unless you see clear side effects about acute kidney injury. In those cases I would, of course, recommend to discontinue the medication.

We are working on more analyses around the eGFR dip, and I expect that you will see a full disclosure of all the data in the next couple of months.

So this was Hiddo Heerspink from ASN Kidney Week 2025. I thank you for listening, and I hope you find these new data useful for your clinical practice.

Announcer:
Thank you for listening to this DataPulse from ASN Kidney Week 2025 on ReachMD. This activity is provided by Medcon International. Thank you for listening.