Abstract
BACKGROUND: Semaglutide and other Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated cardiovascular and renal benefits in patients with type 2 diabetes mellitus (T2DM); however, individuals with end-stage renal disease (ESRD) have been systematically excluded from landmark outcome trials. Consequently, real-world data evaluating the safety and effectiveness of GLP-1 RAs in this high-risk population remain limited. METHODS: This multicenter retrospective cohort study evaluated adult patients with T2DM and ESRD, including those receiving maintenance hemodialysis, who were prescribed injectable semaglutide between January 2016 and July 2025 at tertiary care centers in Saudi Arabia. The primary efficacy outcomes were changes in glycemic control and insulin requirements following initiation of injectable semaglutide. Secondary outcomes included changes in body weight. Safety outcomes comprised acute kidney injury (AKI), severe hypoglycemia, treatment discontinuation due to adverse events, expanded major adverse cardiovascular events (MACE), and all-cause mortality. RESULTS: Seventeen patients were included, with a median follow-up of 1,187 days (IQR 602-1,442); 58.8% were receiving hemodialysis. Mean HbA1c decreased from 9.06 ± 1.69% to 8.75 ± 2.48% (-0.31 ± 2.57%; p = 0.630), with insulin dose reductions observed among the subset of patients with available documentation. Among 16 patients with paired weight measurements, mean body weight decreased by -12.63 ± 24.03 kg (p = 0.074). No cardiovascular deaths, nonfatal myocardial infarctions, or nonfatal strokes were observed. Three expanded MACE events, all hospitalizations for heart failure, occurred during follow-up. AKI occurred in 57.1% of non-dialysis patients, and severe hypoglycemia was reported in two patients (11.8%). CONCLUSIONS: In real-world practice, injectable semaglutide was associated with descriptive changes in metabolic parameters in patients with ESRD, including those on hemodialysis. Larger prospective studies are needed to better define the role of GLP-1 RAs in this underrepresented population.