Kidney Week

Abstract: TH-OR081

Potential of Triple Therapy in Diabetic Kidney Disease

Session Information

• Precision Medicine in Diabetic Kidney Disease: Biomarkers, Combination Therapies, and Treatment Response Prediction
  November 06, 2025 | Location: Room 372A, Convention Center
  Abstract Time: 05:50 PM - 06:00 PM

Category: Diabetic Kidney Disease

• 702 Diabetic Kidney Disease: Clinical

Authors

• Alkhatib, Lean, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States

Lean Alkhatib, MD

• Saleh, Mohamad, University of Colorado System, Denver, Colorado, United States

Mohamad Saleh, PhD, CAE

• Kadoumi, Obada, Jordan University of Science and Technology, Irbid, Irbid Governorate, Jordan

Obada Kadoumi, MD

• Omaish, Rahaf, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States

Rahaf Omaish, MD

• Arthur, John M., University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States

John M. Arthur, MD, PhD, FASN

Background

Chronic kidney disease (CKD) is a serious complication of type 2 diabetes mellitus (T2DM). While renin-angiotensin system inhibitors (RASi) have long been standard treatment, sodium-glucose cotransporter-2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP-1 RAs) have shown additional renal and cardiovascular benefits. However, the effect of combining all three agents remains unclear.

Methods

We conducted a retrospective cohort study of 18,911 adults with T2DM and CKD or albuminuria treated at UAMS from 2018 to 2025. Patients were stratified by therapy: Monotherapy (MT) with RASi, SGLT2i, or GLP-1 RAs; Dual Therapy (DT) with any two; and Triple Therapy (TT) with all three for ≥6 months. The primary outcome was a composite of ≥50% sustained decline in eGFR, end-stage kidney disease (ESKD), or all-cause mortality. Secondary outcome included changes in eGFR slope and urine albumin creatinine ratio (UACR). Multivariable models were adjusted for confounders, including baseline eGFR.

Results

Of 18,911 patients (MT (N=14,092); DT (N=2,450); TT (N=2,369)), TT had a significantly lower risk of the primary outcome vs. MT (HR 0.60; 95% CI 0.38–0.95; P=0.029) but not vs. DT (HR 0.80; P=0.240). TT was associated with a significantly slower eGFR decline (1.2 vs. 2.1 and 3.5 mL/min/1.73m²/year for DT and MT, respectively; P<0.001 for both comparisons). A subgroup analysis of the TT group, restricted to baseline eGFR < 60 mL/min/1.73m², showed consistently significant results with a mean annual eGFR decline (1.5 mL/min/1.73m²/year vs. 2.1 for DT (P = 0.012); and vs. 3.5 for MT (P < 0.001)). The reduction in UACR was significantly greater in the TT group regardless of baseline UACR; (For a ≥ 300 mg/g baseline: 60% vs. 45% and 25% for DT and MT, respectively; P<0.001 for trend) and (For a < 300 mg/g baseline: 50% vs. 40% and 22% for DT and MT, respectively; P<0.001 for trend).

Conclusion

TT was significantly linked to slower annual eGFR decline and greater UACR reduction compared to DT and MT. However, its benefit over DT in the primary outcome was not statistically significant. These findings support the potential renoprotective benefits of TT in diabetic kidney disease.

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025pt4vchxa