Abstract 4139027: Glucagon-like Peptide-1 Receptor Agonist Use and Cardiac Outcomes in Patients with End Stage Kidney Disease

Background: Despite the substantial cardiovascular (CV) risk experienced by people with end-stage kidney disease (ESKD), few medications improve CV outcomes in this population. Glucagon-like peptide-1 receptor agonists (GLP1RA) improve CV outcomes in CKD, and several are safe for use in ESKD, but no outcomes trial has studied GLP1RA in ESKD. We hypothesize that CV outcomes will be improved in people with ESKD and type 2 diabetes mellitus (T2D) who initiated GLP1RA as compared to dipeptidyl peptidase-4 inhibitors (DPP4i), an agent that comparably lowers glucose but has not been shown to improve CV outcomes. Methods: We analyzed electronic health records, claims, and Medicare Part D data from the United States Renal Data System between 2011 and 2021 to identify new users of GLP1RA or DPP4i after initiation of dialysis. We restricted the cohort to patients with T2D based on ICD codes and used 2:1 propensity score matching of DPP4i to GLP1RA users based on 22 covariates. The primary outcome was a modified major adverse cardiovascular events (MACE) composite of myocardial infarction (MI), stroke, and all-cause mortality. We applied cause-specific Cox proportional hazard models and Fine-Gray subdistribution hazard models to account for competing risks to analyze the primary outcome and its components. Results: The matched cohort included 10,196 DPP4i and 5976 GLP1RA initiators. The median age was 59 years, 49% were women, and 29% were of Black race. Compared to DPP4i initiators, GLP1RA initiators experienced a significantly lower risk of MACE (HR 0.92, 95% CI 0.89 – 0.96; Table). The risk of nonfatal MI or stroke was also significantly lower for GLP1RA initiators (HR 0.91, 95% CI 0.87-0.95). All-cause mortality did not differ based on cause-specific hazard modeling (HR 0.97, 95% CI 0.88-1.06), but was significant based on subdistribution hazard modeling (HR 0.86, 95% CI 0.79-0.94). Conclusion: Initiation of GLP1RA was associated with significantly lower risk of MACE in patients with T2D and ESKD compared to DPP4i.