BACKGROUND: Cardiovascular disease is a leading cause of post-transplant mortality in kidney transplant recipients (KTRs), especially those with diabetes. Although glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated cardiovascular and kidney benefits in the general population with type 2 diabetes mellitus (T2DM), evidence regarding their effects in diabetic KTRs is limited. METHODS: This retrospective cohort study utilized data from the Global Collaborative Network in TriNetX, spanning January 1, 2006, to June 1, 2023. Propensity score matching (PSM) with 1:1 ratio was employed to create balanced cohorts. Adult KTRs with T2DM who received GLP-1 RAs within 3 months post-transplant were compared to a matched cohort of KTRs who did not. The primary outcome was all-cause mortality, with secondary outcomes including major adverse cardiovascular events (MACEs) and major adverse kidney events (MAKEs). RESULTS: A total of 35,488 adult KTRs with T2DM (mean [SD] age, 57.7 [12.2] years
57.7% men) were identified and 9.8% patients used GLP-1 RAs among 3 months post-transplant. Following PSM, 3564 GLP-1 RAs users were matched with an equal number of nonusers. After a median follow-up of 2.5 years, GLP-1 RAs users had lower risks of mortality (adjusted hazard ratio (aHR), 0.39
95% CI 0.31-0.50), MACEs (aHR 0.66
95% CI 0.56-0.79), and MAKEs (aHR 0.66
95% CI 0.58-0.75). Adverse effects included higher risks of nausea, vomiting and diarrhea, while risks of suicide, hypoglycemia, retinopathy, and pancreatitis were not increased. CONCLUSIONS: In KTRs with T2DM, GLP-1 RAs use was associated with substantial reductions in all-cause mortality, MAKEs, and MACEs compared to nonuse without increasing complications. However, the underutilization of GLP-1 RAs represents a significant opportunity to improve post-transplant outcomes in this high-risk population.