Abstract: SA-PO0413
GLP-1 Receptor Agonists vs. Dipeptidyl-Peptidase 4 (DPP-4) Inhibitors in Patients with Diabetes, ESKD, and Heart Failure on Dialysis: A Target Trial Emulation
Session Information
- CKM: Clinical - Epidemiology and Outcomes
October 24, 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
- Yu, Chih-Hen, National Cheng Kung University College of Medicine, Tainan City, Taiwan
- Liu, Po-Yi, National Cheng Kung University College of Medicine, Tainan City, Taiwan
- Lai, Edward, National Cheng Kung University College of Medicine, Tainan City, Taiwan
- Sung, Junne-Ming, National Cheng Kung University College of Medicine, Tainan City, Taiwan
Background
Patients with diabetic ESKD and HF have extreme cardiovascular risk but are largely excluded from randomized trials. Whether GLP-1RAs reduce cardiovascular and HF events in this population is unknown.
Methods
Using the multinational TriNetX network, we emulated a new-user, active-comparator target trial of GLP-1RA vs DPP-4i initiation in adults with diabetes, ESKD, and HF. ESKD was defined by N18.6, excluding transplant status, with dialysis certainty characterized by dialysis-related codes and a confirmatory N18.6+Z99.2 subset. After 1:1 propensity score matching, 2-year outcomes were assessed. Robustness was examined using multivariable Cox models, prespecified subgroups, sustained-exposure analyses, negative/positive controls, and healthcare-engagement proxies.
Results
Among 5,360 eligible new users, 1,388 GLP-1RA initiators were matched to 1,388 DPP-4i initiators with balanced covariates. GLP-1RA initiation was associated with lower risk of the primary composite outcome (ischemic cardiovascular events plus HF exacerbation: 31.7% vs 41.4%; HR 0.724, 95% CI 0.640–0.820; p<0.0001), ischemic cardiovascular events (HR 0.737), HF exacerbation (HR 0.760), all-cause mortality (HR 0.680), hospitalization (HR 0.743), and a death-inclusive composite (HR 0.716). In the confirmatory dialysis-dependence-coded HF subset (773 matched pairs), the association remained consistent for the primary outcome (29.9% vs 39.7%; HR 0.716, 95% CI 0.604–0.850; p=0.0004). Findings were consistent across LVEF-documented, prior-event, and incident/prevalent HF strata, with robust bias probes and death-inclusive analyses.
Conclusion
GLP-1RA initiation was associated with lower cardiovascular events, HF exacerbation, and mortality than DPP-4i initiation in diabetic ESKD with HF, a high-risk population with limited therapeutic evidence. These hypothesis-generating findings support randomized evaluation.
Funding
- Government Support – Non-U.S.