S2634 GLP-1 Receptor Agonist Use Is Associated With Lower Risks of Cardiovascular and Kidney Outcomes in Type 2 Diabetic Liver Transplant Recipients

Introduction: Cardiovascular disease remains a leading cause of post‐transplant mortality among liver transplant (LT) recipients after acute phase, particularly in those with diabetes. Glucagon‐like peptide‐1 receptor agonists (GLP-1 RAs) have demonstrated both cardiovascular and renal benefits in the general population with type 2 diabetes mellitus (T2DM), their effects in diabetic LT recipients remain unclear. Methods: We performed a retrospective cohort study using US collaborative Network within TriNetX, from January 1, 2014, to December 31, 2023. Adult LT recipients (≥18 years) with preexisting type 2 diabetes who started a GLP-1 RA within 6 months post‐transplant were compared to propensity-score matched diabetic recipients who did not receive GLP-1 RAs. Recipients who died within 3 months or had incomplete follow-up were excluded. Matching factors included demographics, comorbidities, lab values, and concurrent medications. The primary outcome was all-cause mortality within 5 years. Secondary outcomes were new major adverse cardiovascular events (MACEs) and major adverse kidney events (MAKEs), defined as new dialysis dependence. Subgroup analyses were stratified by BMI (<30 vs ≥30). Adjusted hazard ratios and 95% confidence intervals were estimated using Cox models, with proportional hazards assumptions tested by the Schoenfeld method. Negative control outcomes were herniated discs and trauma. Results: Among 31,391 LT recipients with T2DM, 2,507 (8%) initiated a GLP-1 RA within 6 months post-transplant. After PSM, 2,274 GLP-1 RA users (mean [SD] age, 60.3 ± 10.2 years; 37.7% woman) were compared 1:1 with non-users (60.1 ± 10.8 years; 37.1% woman). Over a median follow-up of 3 years, GLP-1 RAs users were associated with significant lower risks of mortality (aHR: 0.448; 95% CI 0.377–0.534), a composite of MACEs (aHR: 0.719; 95% CI 0.594–0.869) including acute myocardial infarction (aHR: 0.748; 95% CI, 0.578-0.967), heart failure (aHR:0.802; 95% CI, 0.654-0.984), and MAKEs (aHR: 0.503; 95% CI 0.381–0.664) compared with GLP-1 RAs non-users. No significant differences were found in stroke including cerebral infarction or nontraumatic brain injury (aHR: 0.757; 95% CI, 0.556–1.031) nor negative outcome controls including trauma (aHR: 0.865; 95% CI, 0.653-1.144) and HIVD (aHR: 1.177; 95% CI, 0.984-1.408). Conclusion: In LT patients with T2DM, GLP-1 RAs use was associated with significant reductions in all-cause mortality, MAKEs, and MACEs compared to nonuser.