QUARTET-DKD: Quadruple Therapy for Type 2 Diabetic Nephropathy

What this study is testing ClinicalTrials.gov NCT07775846 ↗

Description as written by the study sponsor.

This study employs a prospective, randomized, double-blind, parallel-controlled design, aiming to enroll adult participants with type 2 diabetic kidney disease (DKD) who meet the eligibility criteria. With an angiotensin receptor blocker (ARB) as the background therapy, all participants will be randomized in a 1:1:1:1 ratio into four treatment groups: Group 1 (G1): ARB + empagliflozin + finerenone placebo + mazdutide placebo; Group 2 (G2): ARB + empagliflozin + finerenone + mazdutide placebo; Group 3 (G3): ARB + empagliflozin + mazdutide + finerenone placebo; Group 4 (G4): ARB + empagliflozin + mazdutide + finerenone. The primary comparisons include G2 vs. G1, G3 vs. G1, G4 vs. G2, and G4 vs. G3, designed to evaluate the superiority of triple therapy over dual therapy, and quadruple therapy over triple therapy, in reducing the urine albumin-to-creatinine ratio (UACR).

Treatments tested

• empagliflozin Drug

  Oral tablet, administered at a fixed dose of 10 mg once daily for 6 months.

• Finerenone Drug

  Oral tablet, taken once daily for 6 months. Initial dose is 10 mg or 20 mg once daily adjusted based on baseline eGFR (20 mg for eGFR \>= 60 mL/min/1.73m²; 10 mg for eGFR 30-60 mL/min/1.73m²). Subsequent dose adjustments are guided by serum potassium levels and renal function.

• Mazdutide Drug

  Once-weekly subcutaneous injection for 6 months, following a mandatory dose-escalation schedule: initiated at 2 mg once weekly for 4 weeks, up-titrated to 4 mg once weekly for 4 weeks (if tolerated), and further increased to 6 mg once weekly as the target maintenance dose.

• Finerenone Placebo Drug

  Oral tablet matching active finerenone in appearance and scheduling, without active ingredients, taken once daily for 6 months.

• Mazdutide Placebo Drug

  Once-weekly subcutaneous injection matching active mazdutide in appearance and scheduling, without active ingredients, for 6 months.

• Angiotensin Receptor Blocker (ARB) Drug

  Standard background therapy, titrated to a stable dose for at least 4 weeks prior to enrollment and maintained throughout the 6-month study period.