Abstract: SA-PO1158
Target Emulation Trial of GLP-1 Receptor Agonists (GLP-1 RA), SGLT2 Inhibitors (SGLTi), or Dipeptidyl-Peptidase 4 Inhibitors (DPP4i) as Add-On Therapy in Primary Prevention of Kidney Outcomes Among Older Veterans
Session Information
- CKD: SGLT2 Inhibitors and GLP-1 RAs for Kidney Health
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials
Authors
- Hung, Adriana, VA Tennessee Valley Healthcare System, Nashville, Tennessee, United States
- Beck, Cole A, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Greevy, Robert, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Hackstadt, Amber J., Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Elasy, Tom A., Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Roumie, Christianne, VA Tennessee Valley Healthcare System, Nashville, Tennessee, United States
Background
Kidney disease is a common diabetes complication. We evaluated three medications, GLP1RA, SGLT2i, and DPP4i, on the association with kidney disease, particularly among older Veterans under-represented in clinical trials.
Methods
We assembled a retrospective cohort of Veterans with diabetes combining data from Veterans Affairs, Medicare, and National Death Index databases. Veterans who added either GLP1RA, SGLT2i, or DPP4i to their regimen were followed until 50% decline in estimated glomerular filtration rate (eGFR), ESKD, death, or were censored for non-persistence of that drug class, loss of follow-up, and study end. Follow-up was truncated at 5 years. The primary analyses used three-way propensity weighting to compare the cause-specific hazard of a kidney event or death between treatments. A secondary analysis considered the cause-specific hazard of kidney events with death as a censoring event. An Aalen Johansen plot evaluated death as a competing risk. Subgroup analysis evaluated Veterans by age and baseline eGFR.
Results
After propensity weighting, the cohort included 42,684 GLP1RA, 44,198 SGLT2i and 44,213 DPP4i episodes. Median age was 69 years, diabetes duration 10.6 (6.8, 15.2) years, and eGFR was 74.8 [57.7, 92.3], 62% of Veterans had the medication added as a third agent. In the analyses event rates per 1000 person years were 34.6 (33.3, 36.0) vs 29.0 (27.8, 30.3) vs. 47.4 (46.0, 48.9) for GLP1RA, SGLT2i and DPP4i respectively. Adjusted hazard ratios demonstrated a protective association for kidney events and death compared to DPP4 for both GLP1RA [0.70 (0.67, 0.74)] and SGLT2i users [0.65 (0.61, 0.68)]. Results were similar for evaluation of cause-specific hazard of kidney events-GLP1RA [0.72 (0.65, 0.80)] and SGLT2i [0.48 (0.43, 0.55)]. Results were consistent among subgroups including age >65 years [0.75 (0.66, 0.85)] and [0.61 (0.57, 0.75)] and those with normal eGFR [0.69 (0.64, 0.73)] and [0.51 (0.44, 0.60)] for GLP1RA and SGLT2i respectively .
Conclusion
Both GLP1RA and SGLT2i as add-on treatment for diabetes were associated with a reduced cause-specific hazard of kidney outcomes and death compared to DPP4i. This benefit was similar across subgroups, highlighting the value in primary prevention and the older population.
Funding
- Veterans Affairs Support