Background: Atherosclerotic cardiovascular disease is the leading cause of death in people with type 2 diabetes (T2D) and chronic kidney disease (CKD) or end-stage kidney disease (ESKD). Glucagon-Like Peptide-1 receptor agonists (GLP-1RA) reduce cardiovascular events, improve glycemic control, promote weight loss, and slow progression of nephropathy. Despite these benefits and professional society treatment guidelines recommendations, GLP-1RAs remain under-utilized in people with advanced CKD and ESKD due to tolerability and safety concerns., Methods: We conducted a retrospective cohort study comparing clinical outcomes and medication use details after initiating GLP-1RA or dipeptidyl-peptidase 4 inhibitor (DPP-4i) in people with T2D and advanced CKD or ESKD. Eligible patients were identified via electronic health record query with extraction of baseline demographics, vital signs, and laboratory values. A manual chart review was undertaken to confirm eligibility, medication use, and extract a detailed account of all side effects., Results: A total of 236 eligible patients (149 in the GLP-1RA group and 87 in the DPP-4i group) were identified. The average duration of treatment was 1036 (±909.9) and 1109 (±1090.9) days for GLP-1RA and DPP-4i, respectively. The average percentage weight loss from baseline to 36 months of treatment in the GLP-1RA group was -9.6 % (95 % CI, -11.3 to -7.8) versus -2.4 % (95 % CI, -5.4 to 0.5) in the DPP-4i group (estimated treatment difference (ETD) -7.1 (95 % CI, -10.6 to -3.7) percentage-points, p < 0.001). The change in HbA1c from baseline to 36 months of treatment was significantly greater in the GLP-1RA (-1.0 %) compared with the DPP-4i group (0.2 %) (ETD -1.2 (95 % CI, -2.1 to -0.3) percentage-points, p = 0.04)., Conclusion: In patients with T2D and advanced CKD or ESKD, treatment with GLP-1RAs in a real-world setting had long treatment persistence, and compared to DPP-4is, was associated with greater weight loss and glycemic improvement., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Donglu Xie reports financial support was provided by National Center for Advancing Translational Sciences. Ildiko Lingvay reports a relationship with Novo Nordisk that includes: consulting or advisory and funding grants. Ildiko Lingvay reports a relationship with Sanofi that includes: consulting or advisory and funding grants. Ildiko Lingvay reports a relationship with Merck that includes: consulting or advisory and funding grants. Ildiko Lingvay reports a relationship with Pfizer that includes: consulting or advisory and funding grants. Ildiko Lingvay reports a relationship with Mylan that includes: consulting or advisory and funding grants. Ildiko Lingvay reports a relationship with Boehringer Ingelheim that includes: consulting or advisory and funding grants. Ildiko Lingvay reports a relationship with Eli Lilly that includes: consulting or advisory. Ildiko Lingvay reports a relationship with AstraZeneca that includes: consulting or advisory. Ildiko Lingvay reports a relationship with Janssen that includes: consulting or advisory. Ildiko Lingvay reports a relationship with Intercept that includes: consulting or advisory. Ildiko Lingvay reports a relationship with Intarcia that includes: consulting or advisory. Ildiko Lingvay reports a relationship with TargetPharma that includes: consulting or advisory. Ildiko Lingvay reports a relationship with Novartis that includes: consulting or advisory. Ildiko Lingvay reports a relationship with GI Dynamics that includes: consulting or advisory. Ildiko Lingvay reports a relationship with MannKind that includes: consulting or advisory. Ildiko Lingvay reports a relationship with Valeritas that includes: consulting or advisory. Ildiko Lingvay reports a relationship with Carmot that includes: consulting or advisory. Ildiko Lingvay reports a relationship with Zealand Pharma that includes: consulting or advisory. Ildiko Lingvay reports a relationship with Shionogi that includes: consulting or advisory. Ildiko Lingvay reports a relationship with Mediflix that includes: consulting or advisory. Ildiko Lingvay reports a relationship with Bayer that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)