Kidney Week

Abstract: FR-OR019

Kidney Failure Risk Modifies Comparative Effectiveness of SGLT2 Inhibitors and GLP-1 Receptor Agonists on Cardiovascular-Kidney-Metabolic (CKM) Events

Session Information

• CKD: Identifying Risks and Optimizing Outcomes
  November 07, 2025 | Location: Room 362A, Convention Center
  Abstract Time: 04:30 PM - 04:40 PM

Category: CKD (Non-Dialysis)

• 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

• Hartsell, Sydney Elizabeth, Cardio-Renal Metabolism Center, Univ Utah, Salt Lake City, Utah, United States

Sydney Elizabeth Hartsell, MD, MPH

• Wei, Guo, Cardio-Renal Metabolism Center, Univ Utah, Salt Lake City, Utah, United States

Guo Wei, MS

• Singh, Ravinder, Cardio-Renal Metabolism Center, Univ Utah, Salt Lake City, Utah, United States

Ravinder Singh, MS

• Throolin, Michael J, Cardio-Renal Metabolism Center, Univ Utah, Salt Lake City, Utah, United States

Michael J Throolin, MS

• Nevers, Mckenna R., Cardio-Renal Metabolism Center, Univ Utah, Salt Lake City, Utah, United States

Mckenna R. Nevers, MSc

• Akramimoghadam, Farideh, Cardio-Renal Metabolism Center, Univ Utah, Salt Lake City, Utah, United States

Farideh Akramimoghadam

• Derington, Catherine G., University of Colorado Anschutz Medical Campus School of Medicine, Aurora, Colorado, United States

Catherine G. Derington, PharmD, MS

• Sarwal, Amara, Cardio-Renal Metabolism Center, Univ Utah, Salt Lake City, Utah, United States

Amara Sarwal, MD

• Boucher, Robert E., Cardio-Renal Metabolism Center, Univ Utah, Salt Lake City, Utah, United States

Robert E. Boucher

• Shen, Jincheng, PHS Dept, Univ Utah, Salt Lake City, Utah, United States

Jincheng Shen, MS, PhD

• Drakos, Stavros, Cardio-Renal Metabolism Center, Univ Utah, Salt Lake City, Utah, United States

Stavros Drakos, MD, PhD

• Greene, Tom, PHS Dept, Univ Utah, Salt Lake City, Utah, United States

Tom Greene, PhD

• Beddhu, Srinivasan, Cardio-Renal Metabolism Center, Univ Utah, Salt Lake City, Utah, United States

Srinivasan Beddhu, MD

Background

A better understanding of heterogeneity within CKM syndrome is a research priority. Whether kidney failure risk modifies the comparative effectiveness of SGLT2i vs. GLP-1RA is clinically important.

Methods

We conducted an active comparator, new user study of SGLT2i, GLP-1RA and insulin glargine (IG) in a national cohort of veterans with T2D on metformin who started a study drug 2018-2021 (N=160,428). 5-year kidney failure risk equation (KFRE) score was calculated using age, sex, eGFR and UACR. Follow-up was through 3/31/23. Kidney failure (Stage V CKD by follow-up eGFR or ESKD by ICD codes and USRDS linkage), MACE (HF, MI or stroke ICD codes), CKM composite (kidney failure or MACE) and all-cause death were outcomes. We related SGLT2i vs GLP-1RA initiation with subsequent outcomes in separate inverse probably weighted Cox regression models within each KFRE subgroup (<2%, 2-<6%, ≥6%, and missing). We compared regression coefficients of SGLT2i vs. GLP-1RA in KFRE 2-<6% vs. ≥6% with Wald tests to examine effect modification.

Results

IG (N=54,015) had higher risk compared to either SGLT2i (N=84,625) or GLP-1RA (N=21,788) consistently. Compared to GLP-1RA, SGLT2i had significantly higher hazard of kidney failure, MACE and CKM composite and equivalent hazard of death in KFRE 2-<6% group. In KFRE ≥6%, SGLT2i had non-significantly lower hazard of kidney failure, MACE, CKM composite and death (Figure). There was significant effect modification of SGLT2i vs. GLP-1RA comparisons by KFRE risk groups 2-<6% vs. ≥6% for kidney failure (p=0.002), MACE (p=0.004), and CKM composite (p=0.006).

Conclusion

We present novel evidence that KFRE scores modify the real-world comparative effectiveness of SGLT2i vs. GLP-1RA on kidney failure and CKM outcomes in T2D, favoring GLP-1RA in KFRE 2-<6% and SGLT2i in KFRE ≥6%.

Funding

• NIDDK Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025gvpshbjk