QUARTET-DKD: Quadruple Therapy for Type 2 Diabetic Nephropathy

Prior treatment

• Refractory hypertension, defined as a resting SBP \> 170 mmHg despite the concurrent use of three antihypertensive medications.
• History of severe dehydration, severe diarrhea, or acute volume depletion within 30 days prior to screening.
• History of acute kidney injury (AKI) within 30 days prior to screening.
• Use of traditional Chinese medicines with potential proteinuria-lowering effects (e.g., Keluoxin capsules, Huangkui capsules, or Shenyan Kangfu tablets) within 30 days prior to screening.
• Use of GLP-1 receptor agonists, GLP-1/GIP dual receptor agonists, or GLP-1/glucagon (GCG) dual receptor agonists within 6 months prior to screening.
• Current use of strong CYP3A4 inhibitors (e.g., itraconazole or clarithromycin) or CYP3A4 inducers that may significantly interfere with finerenone metabolism.
• Myocardial infarction, unstable angina, stroke, or hospitalization due to heart failure (NYHA Class III-IV) within 3 months prior to screening.
• Active urogenital tract infection, or a history of urogenital tract infection associated with the prior use of SGLT2 inhibitors.

Other illness

• Definite diagnosis of non-diabetic kidney disease (e.g., IgA nephropathy, polycystic kidney disease, lupus nephritis, etc).
• Personal or family history of medullary thyroid carcinoma (MTC), or a diagnosis of multiple endocrine neoplasia syndrome type 2 (MEN 2).
• History of severe acute or chronic pancreatitis.
• History of diabetic ketoacidosis (DKA).
• Inability to complete the 6-month follow-up due to general health conditions or geographic relocation.
• Any other condition that, in the opinion of the investigator, renders the participant unsuitable for participation in the study.

Lab values

• Use of potassium-sparing diuretics (e.g., triamterene or amiloride) or mineralocorticoid receptor antagonists (e.g., spironolactone, eplerenone, or finerenone) within 2 months prior to screening.

Other

• Symptomatic hypotension during the screening period, or a resting systolic blood pressure (SBP) \< 110 mmHg.
• Women who are pregnant, planning to become pregnant, or lactating.

• Age ≥18 years, with a confirmed diagnosis of type 2 diabetes mellitus (T2DM).
• Receiving a standard dose of an Angiotensin-Converting Enzyme Inhibitor (ACEI) or Angiotensin Receptor Blocker (ARB) therapy for at least 4 consecutive weeks prior to screening, with the dose expected to remain stable throughout the study period.
• Body Mass Index (BMI) ≥ 24.0 kg/m2.
• Mean urine albumin-to-creatinine ratio (UACR) ≥ 100 mg/g and \< 5000 mg/g, calculated from first morning void urine samples collected over 3 consecutive days.
• Estimated glomerular filtration rate (eGFR) based on the CKD-EPI formula ≥ 30 mL/min/1.73m2 and ≤ 90 mL/min/1.73m2.
• Serum potassium level ≤ 4.8 mmol/L.
• Glycated hemoglobin (HbA1c) \< 11%.
• Voluntarily understood and signed the written Informed Consent Form (ICF).