Kidney Week

Abstract: FR-PO319

SGLT2 Inhibitors Are Associated with Lower Risk of CKD Progression in Type 2 Diabetes (T2D) than Glucagon-Like Peptide 1 Receptor Agonists (GLP-1 RAs): An Emulated Clinical Trial

Session Information

• Diabetic Kidney Disease: Clinical Modeling, Diagnosis, Education, and More
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 702 Diabetic Kidney Disease: Clinical

Authors

• Hartsell, Sydney Elizabeth, The University of Utah School of Medicine, Salt Lake City, Utah, United States

Sydney Elizabeth Hartsell, MD, MPH

• Sarwal, Amara, The University of Utah School of Medicine, Salt Lake City, Utah, United States

Amara Sarwal, MD

• Singh, Ravinder, The University of Utah School of Medicine, Salt Lake City, Utah, United States

Ravinder Singh, MS

• Nevers, Mckenna R., The University of Utah School of Medicine, Salt Lake City, Utah, United States

Mckenna R. Nevers, MSc

• Shen, Jincheng, The University of Utah School of Medicine, Salt Lake City, Utah, United States

Jincheng Shen, MS, PhD

• Wei, Guo, The University of Utah School of Medicine, Salt Lake City, Utah, United States

Guo Wei, MS

• Boucher, Robert E., The University of Utah School of Medicine, Salt Lake City, Utah, United States

Robert E. Boucher

• Greene, Tom, The University of Utah School of Medicine, Salt Lake City, Utah, United States

Tom Greene, PhD

• Drakos, Stavros, The University of Utah School of Medicine, Salt Lake City, Utah, United States

Stavros Drakos, MD, PhD

• Beddhu, Srinivasan, The University of Utah School of Medicine, Salt Lake City, Utah, United States

Srinivasan Beddhu, MD

Background

There is a paucity of data on head-to-head comparisons between GLP1-RA and SGLT2i on the risk of CKD progression in T2D.

Methods

We used an active comparator, new user design to compare insulin glargine (IG), GLP1-RA and SGLT2i among veterans with T2D and CKD (eGFR <60) on metformin who initiated one of these drugs between 01/01/18 and 12/31/21 (N=26,624). Generalized propensity score based inverse probability weighting (IPW) was used to minimize confounding in comparisons across the three drug classes. Outcomes were CKD progression (50% eGFR drop or eGFR <15 sustained over 2 consecutive labs), all-cause mortality (ACM) and renal/ACM composite, followed through 3/31/23. We will add ESRD data with follow-up until 12/21 via USRDS linkage when available July 2024. IPW Cox regression models related study drug class to kidney and mortality outcomes, additionally adjusted for demographics, comorbidities, diabetes severity, and baseline labs and medications.

Results

Prior to weighting, 9,829, 3,799 and 12,996 veterans initiated IG, GLP1-RA and SGLT2i respectively with baseline eGFRs of 48.7(9.0), 48.8(8.0) and 51.1(6.7) ml/min/1.73m², mostly in Stage 3A (73.3%, 72,6% and 83.3% respectively). Few had albuminuria >300mg/g (7.7%, 7.7% and 8.2% at baseline) but most did not have urine albumin lab data available within 365 days prior to study drug initiation date (41-46% missing across all groups). Pairwise comparisons of unweighted and weighted event rates and hazard ratios are shown in the table. Compared to those on GLP1-RA, veterans with T2D and CKD on SGLT2i had a 39% lower hazard of 50% decrease in eGFR or progression to CKD Stage V (HR 0.61, 95%CI 0.49-0.75) and a 22% lower hazard of renal/ACM (HR 0.88, 95%CI 0.79-0.98). IG was associated with a higher risk of CKD progression compared to SGLT2i or GLP1-RA.

Conclusion

These data from a large national cohort of veterans with T2D and CKD suggest that SGLT2i may have a renoprotective advantage over GLP1-RA.

Table

Funding

• NIDDK Support