GLP-1 Receptor Agonist Outcomes, Safety, and BMI Change in a National Cohort of Dialysis Patients

Background: Of the 808,000 US dialysis patients, 60% have diabetes and are eligible for glucagon-like peptide-1 (GLP-1) receptor agonists. Safety and outcomes in this population is unknown. We sought to examine GLP-1 receptor agonist real-world safety, efficacy, and weight loss in people with diabetes on dialysis. Methods: In this observational national cohort study (2013-2021), we identified adults with type 2 diabetes on dialysis. The exposure of interest was GLP-1 receptor agonist use. Body mass index ( BMI) change after dialysis initiation was quantified among patients with two measurements (N=6,474). Extended Cox models with inverse probability of treatment weights (censoring for kidney transplant waitlisting) were used to quantify all-cause mortality associated with GLP-1 receptor agonists. Specific safety outcomes (acute pancreatitis, biliary complications, medullary thyroid cancer, diabetic retinopathy) were assessed. Results: The study included 151,649 incident dialysis patients with type 2 diabetes. Mean BMI and weight change among GLP-1 receptor agonist users were greater than that among non-users (-1.47 versus -0.61 kg/m 2 ; -4.03 versus -1.47 kg; P <0.001 for both). The mortality incidence rate was lower among GLP-1 receptor agonist users (219.0 versus 279.5 cases/1,000 person-years; P <0.001). GLP-1 receptor agonist use was associated with a 23% lower risk of mortality (adjusted hazard ratio [aHR]: 0.77, 95% confidence interval [CI]:0.70-0.85; P <0.001); results were consistent among initiates with BMI≥30 kg/m 2 . GLP-1 receptor agonist use was associated with a 66% higher chance of waitlisting (aHR=1.66, 95%CI:1.28-2.13; P <0.001). There was an increased association with diabetic retinopathy (aHR=1.32, 95%CI:1.12-1.56; P =0.001), but not with any other safety outcomes. Inferences were consistent across multiple sensitivity analyses. Conclusions: GLP-1 receptor agonist use in patients with type 2 diabetes on dialysis was associated with weight loss, reduced mortality risk, and increased likelihood of kidney transplant waitlisting. These real-world data are the strongest evidence to date supporting GLP-1 receptor agonist use in this population.