Document Type
Article
Publication Date
5-28-2026
Abstract
INTRODUCTION: The comparative effectiveness of glucagon-like peptide-1 (GLP-1) agonists (GLP-1s) versus dipeptidyl peptidase-4 (DPP-4) inhibitors (DPP-4s) in hemodialysis is unknown.
METHODS: Using 2011 to 2021 US Renal Data System and Medicare claims data, we emulated a target trial comparing new users of GLP-1s versus DPP-4s with patients who survived ≥ 90 days on in-center hemodialysis before medication initiation. We used inverse probability of treatment weighting (IPTW) and Cox proportional hazards models to estimate hazard ratios (HRs).
RESULTS: We identified 3671 GLP-1 and 12,039 DPP-4 users. After IPTW, mean age was 63 years, 52% male, 63% White, and mean body mass index was 31 kg/m2. The median (interquartile interval) follow-up was 1.5 (0.6-2.9) years. In intention-to-treat analysis, the all-cause mortality HR for GLP-1s (vs. DPP-4s) was 0.98 (95% confidence interval [CI]: 0.89-1.07); cardiovascular mortality HR was 1.06 (95% CI: 0.92-1.23); infection mortality HR: 0.83 (95% CI: 0.54-1.26). In per-protocol analysis with censoring at medication discontinuation, the all-cause mortality HR was 0.81 (95% CI: 0.68-0.96), and the 1-year cumulative incidence of discontinuation was 53% for GLP-1s versus 42% for DPP-4s. The cardiovascular mortality HR was 0.89 (95% CI: 0.69-1.13); infection mortality HR 0.65 (95% CI: 0.37-1.14). Finally, the gastrointestinal symptom HR was 1.11 (95% CI: 1.02-1.20).
CONCLUSION: GLP-1 (vs. DPP-4) initiation was not associated with reduced mortality in intention-to-treat analysis, but continuous use was associated with improved survival. The therapeutic potential of GLP-1s among patients receiving hemodialysis may be limited by medication discontinuation.
Recommended Citation
Le, Dustin; Kilpatrick, Duncan; Kraft, walter K.; Grams, Morgan E.; Jaar, Bernard G.; and Shin, Jung-Im, "Target Trial of Glucagon-Like Peptide-1 Agonists versus Dipeptidyl Peptidase-4 Inhibitors and Mortality in Hemodialysis" (2026). Division of Nephrology Faculty Papers. Paper 14.
https://jdc.jefferson.edu/nephrologyfp/14
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Language
English
Comments
This article is the author’s final published version in Kidney International Reports, Volume 11, Issue 8, 2026, Article number 106618.
The published version is available at https://doi.org/10.1016/j.ekir.2026.106618. Copyright © 2026 The Author(s).