Abstract
BACKGROUND: The advent of glucagon-like peptide-1 receptor antagonists (GLP-1 RAs) has generated significant interest in their potential cardiovascular benefits for patients with type 2 diabetes mellitus (T2DM). However, they lack comprehensive evaluations of their impact on kidney and cardiovascular outcomes in patients with advanced chronic kidney disease (CKD). This study aimed to evaluate the effects of GLP-1 RAs on kidney and cardiovascular outcomes in patients with T2DM and advanced CKD. METHODS: We conducted a retrospective cohort study with a new user design that utilized propensity score matching to establish comparable groups of GLP-1 RA users and nonusers. We obtained data from 69 US healthcare organizations within the TriNetX platform from 1 January 2018 to 31 December 2022. We included 632 308 patients with T2DM, aged ≥18 years, and an estimated glomerular filtration rate of ≤45 mL/min/1.73 m(2), ultimately focusing on 51 910 matched pairs of GLP-1 RA users and nonusers. Cox proportional hazards model was used to evaluate treatment effects on various outcomes. RESULTS: The matched groups had a mean age of approximately 65 years, with men comprising 43% of each cohort. GLP-1 RA users exhibited a significantly lower incidence of dialysis initiation and major adverse cardiovascular events than GLP-1 RA nonusers, with respective hazard ratios (HRs) of 0.89 [95% confidence interval (CI) 0.85-0.93] and 0.92 (95% CI 0.88-0.95). Mortality rates were significantly reduced (HR 0.81; 95% CI 0.78-0.84). Moreover, GLP-1 RA users had significant cardiovascular benefits, which were consistent across subgroup and sensitivity analyses. CONCLUSIONS: GLP-1 RAs were significantly associated with the incidence of kidney and cardiovascular events in patients with T2DM and advanced CKD, suggesting the potential importance of incorporating GLP-1 RA treatment to help modify disease progression and improve survival in this high-risk population.