India Research: Combining Finerenone and Empagliflozin Protects Kidneys in Type 2 Diabetes

A study from India, published in Diabetes Care (2025), offers compelling evidence that using two kidney-protective diabetes medications together — finerenone and empagliflozin — significantly outperforms either drug alone in reducing dangerous protein levels in the urine. Importantly, this benefit holds true even for patients already taking popular GLP-1 receptor agonist medications like semaglutide (Ozempic, Wegovy) or tirzepatide (Mounjaro).

What the CONFIDENCE Trial Found

The CONFIDENCE trial enrolled 800 adults with Type 2 diabetes and chronic kidney disease (CKD). Researchers divided participants into three groups: one group received finerenone alone, one received empagliflozin (an SGLT2 inhibitor) alone, and one received both medications simultaneously. About 23% of all participants — roughly 1 in 4 — were already taking a GLP-1 receptor agonist when the study began.

After 180 days, researchers measured changes in the urinary albumin-to-creatinine ratio (UACR), a key marker of kidney damage. Think of UACR as a leak detector for your kidneys — the higher the number, the more protein is spilling into your urine, signaling kidney stress.

The Numbers in Plain English

For patients already on a GLP-1 medication:

• Combination therapy reduced UACR by 51%
• Finerenone alone reduced UACR by 34%
• Empagliflozin alone reduced UACR by 36%

For patients not on a GLP-1 medication:

• Combination therapy reduced UACR by 56%
• Finerenone alone reduced UACR by 37%
• Empagliflozin alone reduced UACR by 33%

The results were remarkably consistent across both groups, confirming the combination's power regardless of GLP-1 use.

Safety: What About Side Effects?

One common concern with finerenone is elevated potassium (hyperkalemia), which can affect heart rhythm. In this study, hyperkalemia occurred in about 9.0–9.5% of combination therapy patients — similar rates whether or not they used a GLP-1 drug. Acute kidney injury was uncommon in all groups. Blood pressure also decreased, more noticeably in the combination group, which could be an added benefit for many patients with diabetes-related hypertension.

Measurement Conversions for US Patients

The study used eGFR thresholds of 30–90 mL/min/1.73 m² — the same units used by US labs. UACR targets of 100–5,000 mg/g align directly with American Diabetes Association (ADA) CKD staging guidelines, where values above 30 mg/g signal early kidney disease and above 300 mg/g indicate more advanced damage.

How This Compares to US Guidelines

Current ADA Standards of Care (2024) already recommend SGLT2 inhibitors for patients with Type 2 diabetes and CKD, and finerenone is FDA-approved for diabetic kidney disease. However, US guidelines have been cautious about recommending simultaneous initiation of both drugs. This international data strengthens the case for a more aggressive, combination-first approach — particularly for patients with higher UACR levels.

Why This Matters for US Patients

Diabetic kidney disease is the leading cause of kidney failure in the United States, affecting roughly 1 in 3 adults with diabetes. Many US patients are already on GLP-1 medications like Ozempic or Mounjaro — and this study confirms they can safely add finerenone and empagliflozin without losing effectiveness or facing dramatically higher risks. If you have Type 2 diabetes with signs of kidney involvement, ask your doctor whether combination therapy with these agents is appropriate for you. Potassium monitoring will likely be recommended.

Citation: Agarwal R, Green JB, Heerspink HJL, et al. Impact of Baseline GLP-1 Receptor Agonist Use on Albuminuria Reduction and Safety With Simultaneous Initiation of Finerenone and Empagliflozin in Type 2 Diabetes and Chronic Kidney Disease (CONFIDENCE Trial). Diabetes Care. 2025. DOI: 10.2337/dc25-1673. PMID: 40968755.