Kidney Week

Abstract: FR-PO0552

Kidney Outcomes with Combination vs. Individual Cardiorenal Therapy in Adults with Type 2 Diabetes and CKD: A Systematic Review and Structured Evidence Appraisal

Session Information

• CKM: Clinical - Meta-Analyses, Predictive Modeling, Care Delivery, and Safety
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Cardiovascular-Kidney-Metabolic Health

• 602 Cardiovascular-Kidney-Metabolic Health: Clinical

Authors

• Zheng, Jacob Sun, Skyline High School, Ann Arbor, Michigan, United States

Jacob Sun Zheng

• Zheng, Lucy, Mount Sinai Morningside Hospital, New York, New York, United States

Lucy Zheng, MD

• Tan, Wenchy, Mount Sinai Morningside Hospital, New York, New York, United States

Wenchy Tan, MD, MS

• Deb, Mrittika, Mount Sinai Morningside Hospital, New York, New York, United States

Mrittika Deb, DO

• Tan, Samuel, Icahn School of Medicine at Mount Sinai Department of Medicine, New York, New York, United States

Samuel Tan, MD, PharmD

• Lee, Maximillian, UPMC Harrisburg, Harrisburg, Pennsylvania, United States

Maximillian Lee, DO

Background

GLP-1 receptor agonists (GLP-1RA), SGLT2 inhibitors (SGLT2i), and nonsteroidal mineralocorticoid receptor antagonists (ns-MRA) each slow kidney disease progression in adults with type 2 diabetes (T2D) and chronic kidney disease (CKD). Whether combining these agents adds kidney benefit beyond individual therapy remains uncertain.

Methods

We searched MEDLINE, Embase, Cochrane CENTRAL, and ClinicalTrials.gov through April 2026 for randomized trials, subgroup analyses, observational studies, and modeling studies evaluating GLP-1RA, SGLT2i, and/or ns-MRA combinations versus individual agents in adults with T2D and CKD. Outcomes included hard kidney composites, eGFR slope, and urinary albumin-to-creatinine ratio (UACR). Certainty was assessed with GRADE across six prespecified comparisons.

Results

For SGLT2i plus ns-MRA versus monotherapy, the phase 2 CONFIDENCE trial (n=800) showed the combination reduced UACR by 29% more than finerenone alone and 32% more than empagliflozin alone at 180 days (certainty: LOW; surrogate endpoint only; hard kidney outcomes not assessed). For GLP-1RA plus SGLT2i versus monotherapy, a meta-analysis of 3 outcome trials (n=17,072) found GLP-1RA kidney benefits were consistent regardless of baseline SGLT2i use, including an eGFR slope improvement of ~0.75 mL/min/1.73m²/year in SGLT2i users (P-heterogeneity=0.94; certainty: LOW; indirect evidence from subgroup analyses). For GLP-1RA plus ns-MRA and triple combination therapy, evidence was limited to post-hoc subgroup analyses (FIDELITY; n=167 on triple therapy) and a single real-world cohort (n=51), demonstrating consistent UACR reductions but with no dedicated randomized data (certainty: VERY LOW). No randomized trial has evaluated any combination regimen on hard kidney outcomes, including kidney failure, sustained eGFR decline ≥40%, or kidney-related death.

Conclusion

Evidence supporting combination cardiorenal therapy for kidney outcomes in T2D and CKD is limited to surrogate endpoints, short follow-up, and small subgroup analyses, with LOW to VERY LOW certainty across comparisons. The GLP-1RA plus ns-MRA combination and triple therapy remain entirely unaddressed by dedicated trials. Randomized trials evaluating combination regimens on hard kidney outcomes are urgently needed to guide clinical practice.