Le_2026_Kidney.Int.Rep_11_106618

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/m(2). 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.