#1608 Glucagon-like peptide-1 receptor agonists and the risk of emergency department visits and hospitalization in patients across the spectrum of kidney disease

Abstract Background and Aims Glucagon-like-peptide-1 receptor agonists (GLP1RA) have emerged as a therapy that promotes weight loss and confers cardiorenal protection. While recent trials have suggested benefit on heart failure hospitalizations; their effects on all-cause emergency department (ED) visits and hospitalizations have not been well characterized. In this population-based study we examined the effect of initiating a GLP1RA versus a dipeptidyl peptidase 4 inhibitor (DPP4i) on ED visits and all-cause hospitalization in patients across the spectrum of chronic kidney disease (CKD). Method This retrospective cohort study was conducted in Ontario, Canada, using administrative databases housed at ICES. We included a cohort of patients aged ≥18 years with eGFR <90 ml/min/1.73 m2 who received a first prescription of a GLP1RA or DPP4i through the Ontario Drug Benefit between September 30, 2019 to December 31, 2021. Follow-up extended until June 30, 2022. We used inverse probability of treatment weighting (IPTW) based on a propensity score conditioned on 72 covariates to address confounding. We evaluated the effect of GLP1RA initiation on all cause ED visits and hospitalization using time-to-recurrent-event approaches with the Prentice-Williams-Peterson (PWP) gap time model which assumes an event-specific hazard for each ED encounter or hospitalization. In an additional analysis, we evaluated recurrent ED visits and/or hospitalizations using the Andersen-Gill extension of the Cox proportional hazards model and robust sandwich estimators to obtain the 95% confidence intervals. Results The study cohort included 24,576 patients who were new users of a GLP1RA, and 23,600 who were new users of a DPP-4i eGFR <90 ml/min/1.73 m2. Baseline characteristics were balanced between groups (mean age of 69 years, 50% female, 92% with type 2 diabetes mellitus, 3.5% had heart failure, and 41% had CKD stages 3–5). Semaglutide represented 98.4% of GLP1RA prescriptions. Across the cohort, 9.6% had more than one hospitalization while 25.8% had more than one emergency department encounter. Using the PWP gap time model, new use of GLP1RA was associated with a lower risk of all-cause ED encounters or hospitalizations: HR 0.90 (95% CI, 0.87 to 0.94; P < 0.0001). This finding was consistent when we used the calendar time model (HR 0.90; 95% CI, 0.87 to 0.94) or the Andersen-Gill extension of the Cox proportional hazards model (HR 0.87; 95% CI, 0.82 to 0.92) (Table 1). Conclusion In this large population-based study, GLP1RA initiation was associated with a reduction in all-cause ED visits and/or hospitalizations when compared to DPP-4 inhibitor initiation. This finding has potentially substantial implications on health care delivery and resource utilization.

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