Effect of Empagliflozin on Proteinuria in Patients with Type 2 Diabetes and Renal Impairment (eGFR 10-20 ml/min/1.73m2)

The primary objective is to evaluate the anti-proteinuric effect of empagliflozin in patients with type 2 diabetes and an estimated glomerular filtration rate (eGFR) between 10 and 20 ml/min/1.73m2, specifically measuring reductions in the urinary protein-to-creatinine ratio (UPCR). Secondary objectives include assessing the impact on body weight, urinary sodium excretion, urinary volume, and ambulatory blood pressure. Additional evaluations focus on changes in serum potassium and serum bicarbonate levels, the reduction of 24-hour albuminuria, and the comparison of eGFR decrease magnitude between the active treatment and placebo groups. The study also monitors safety markers, including the incidence of acute kidney injury, hyperkalemia, or acidosis, and assesses any effects on HbA1c.

The sponsor did not provide information regarding the total number of participants. The study population consists of male and female patients diagnosed with type 2 diabetes and renal impairment. Eligible participants are aged between 18 and 80 years. Key inclusion requirements include an estimated glomerular filtration rate (eGFR) between 10 and 20 ml/min/1.73m2, a urinary albumin creatinine ratio (UACR) greater than 300 mg/g creatinine, and a urinary protein creatinine ratio (UPCR) greater than 500 mg/g creatinine. Participants must have maintained a maximal tolerated dosage of renin-angiotensin system blockade and a stable dosage of antihypertensive drugs or diuretics for at least one month. Additionally, an office systolic blood pressure exceeding 110 mmHg is required. Women of child-bearing age must have utilized effective contraception for more than one month prior to enrollment, subject to a pregnancy test.

This phase 5 clinical trial is designed to evaluate the anti-proteinuric effect of empagliflozin in patients presenting with type 2 diabetes and renal impairment characterized by an estimated glomerular filtration rate (eGFR) between 10 and 20 ml/min/1.73m2. The study methodology involves the administration of either 10 mg of empagliflozin or a matching placebo. The research aims to measure changes in the urinary albumin creatinine ratio (UACR) and the urinary protein creatinine ratio (UPCR). Study procedures include a screening visit to confirm eligibility based on criteria such as renin-angiotensin system (RAS) blockade, stable antihypertensive medication, and specific urinary albumin levels. Participants will undergo multiple treatment periods, each lasting 6 weeks, with assessments conducted at the end of each period. Secondary endpoints include monitoring changes in body weight, 24-hour urinary sodium excretion, ambulatory systolic blood pressure, serum potassium, serum bicarbonate, and HbA1C. The trial also involves the description of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). The total duration of the study is estimated to span from April 2026 to April 2028.

The experimental treatment consists of empagliflozin administered as 10 mg film-coated tablets. This medication is intended for oral administration.

The control group receives a placebo that is identical in composition to the active medication but lacks the SGLT2 inhibitor active substance.

The efficacy of empagliflozin will be evaluated through several primary and secondary endpoints in patients with type 2 diabetes and renal impairment. The primary assessment focuses on the anti-proteinuric effect by measuring changes in mean urinary albumin-to-creatinine ratio (UACR) and urinary protein-to-creatinine ratio (UPCR). These parameters are determined using spot morning urine samples collected over two consecutive days at baseline and at the conclusion of each 6-week treatment period.

Secondary efficacy parameters include:

• Changes in body weight from baseline to the end of each 6-week treatment period.
• Changes in mean 24-hour urinary sodium excretion and urinary volume, assessed via 3-day urinary collections at baseline and 3 days after the start of each treatment period.
• Changes in mean ambulatory systolic blood pressure measured over 3-day periods at baseline and at the end of each 6-week treatment period.
• Changes in serum potassium and serum bicarbonate levels, monitored weekly throughout each 6-week treatment period.
• Changes in HbA1C from baseline to the end of each 6-week treatment period.
• Changes in mean 24-hour albuminuria, comparing the 3 days following the start of treatment to the 3 days prior to treatment initiation.