A new clinical trial has shown that combining two drugs — an SGLT2 inhibitor and a nonsteroidal mineralocorticoid receptor antagonist — can quickly and significantly reduce signs of kidney damage in patients with type 2 diabetes and chronic kidney disease (CKD).
The randomized CONFIDENCE trial included 818 patients with albuminuria, a condition marked by excess protein in the urine, often signaling kidney problems. Over 180 days, patients who took both empagliflozin (Jardiance) and finerenone (Kerendia) saw a 52% drop in urinary albumin-to-creatinine ratio (UACR), a key marker of kidney function. This result was 29% better than with finerenone alone and 32% better than with empagliflozin alone (P<0.001 for both).
“These findings align with the full additive effect expected from the two drugs,” said Dr. Rajiv Agarwal of the Richard L. Roudebush VA Medical Center, who presented the study at the European Renal Association annual congress. The results were also published in the New England Journal of Medicine.
The UACR dropped fast. After just 14 days of combination therapy, patients had a reduction of over 30%. By day 90, the reduction passed 40%. Even after a 30-day washout period, when treatment stopped, UACR levels remained below baseline in patients who had taken the drug combo or finerenone alone.
The combination treatment helped more patients reach reductions in UACR greater than 30%, 40%, and 50%, compared to those receiving a single drug.
Currently, standard care for patients with type 2 diabetes and CKD includes renin-angiotensin system blockers, SGLT2 inhibitors, mineralocorticoid receptor antagonists, and sometimes GLP-1 receptor agonists. But follow-up testing to measure UACR is often missed in real-world care. Researchers warned that this may delay effective treatment.
“Stepwise therapy can slow down progress and lead to clinical inertia,” the authors noted. “In contrast, starting with combination therapy may lead to faster and larger reductions in UACR.”
However, co-author Dr. Peter Rossing from the University of Copenhagen said the best way to combine these drugs remains unclear, which was the main reason for the trial.
In the double-blind study, patients were randomly assigned to three groups: finerenone alone, empagliflozin alone, or both drugs together. All participants had type 2 diabetes, an eGFR between 30 and 90 mL/min/1.73 m², and a UACR between 100 and 5,000 mg/g. All were already on a renin-angiotensin system blocker. Patients with type 1 diabetes or a kidney transplant were excluded.
Median baseline UACR levels were similar across groups: 574 in the combination group, 578 in the finerenone group, and 583 in the empagliflozin group.
In terms of safety, serum potassium levels rose by 0.27 mmol/L after 14 days of combination therapy but returned to near-baseline 30 days after stopping treatment. Only one patient in each group stopped treatment due to high potassium (hyperkalemia).
A small early drop in estimated glomerular filtration rate (eGFR) was also seen, especially in the combination group, but eGFR nearly returned to baseline after the washout. A drop of more than 30% in eGFR was seen in 6.3% of the combo group, 3.8% of the finerenone group, and 1.1% of the empagliflozin group.
Systolic blood pressure also fell early in treatment but rebounded later. Changes in blood sugar levels (HbA1c) were similar across all groups.
Fewer than 5% of patients in any group stopped treatment due to side effects. Serious events like low blood pressure, acute kidney injury, or hyperkalemia that caused treatment to stop were rare.
The researchers said longer-term follow-up is needed to determine whether the drug combination improves cardiovascular outcomes or slows kidney disease progression.
Related Topics
