GLP-1 receptor agonists in kidney transplant recipients with type 2 diabetes mellitus: a systematic review and meta-analysis on mortality and major adverse kidney events

Abstract

Background Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used in patients with type 2 diabetes mellitus and chronic kidney disease. However, their safety and efficacy in kidney transplant recipients remain uncertain. This study aims to evaluate the impact of GLP-1 RAs on all-cause mortality, major adverse cardiovascular events (MACE), and major adverse kidney events (MAKE) in adult kidney transplant recipients. Methods We conducted a systematic review and meta-analysis of retrospective cohort studies reporting outcomes in adult kidney transplant recipients treated with GLP-1 RAs. A comprehensive search of PubMed, Embase and Cochrane Library was performed up to July 2025. Studies were included if they reported on at least one of the following outcomes: all-cause mortality, MACE, or MAKE. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Results A total of four retrospective cohort studies involving 27,153 were included. A total of 5,479 (20.2%) patients received GLP-1 RAs. The median follow-up period across studies ranged from 1.38 to 3.1 years. GLP-1 RAs treatment was associated with a significant reduction in all-cause mortality, with an aHR of 0.52 (95% CI: 0.32-0.85, I-2 = 86%; p = 0.009). Similarly, a significant reduction in MAKEs was observed, with a pooled aHR of 0.62 (95% CI, 0.53-0.73; I-2 = 15%; p < 0.00001). Conclusions In kidney transplant recipients with type 2 DM, GLP-1 RAs appear to be associated with reduced risks of all-cause mortality and MAKEs. However, given the high heterogeneity across studies and the influence of a single large cohort, these findings should be interpreted with caution and considered exploratory. Prospective studies are needed to confirm the long-term safety and efficacy of GLP-1 RAs in this population.