Sepsis and Infectious Outcomes for GLP-r Agonists in CKD plus Type 2 Diabetes.

BACKGROUND: Chronic kidney disease (CKD) is associated with a higher risk of sepsis and poorer clinical outcomes compared to the general population. While GLP-1 receptor agonists (GLP-1RA) may confer protective effects against sepsis beyond their metabolic benefits in patients with diabetes, their effect in CKD patients remains unclear. This study aims to evaluate the association between GLP-1RA therapy and infectious outcomes in patients with CKD. METHODS: Using the TriNetX database, we conducted a retrospective cohort study of adults with CKD and type 2 diabetes mellitus initiating GLP-1RAs or dipeptidyl peptidase-4 inhibitors (DPP-4i) between January 2020 and May 2026. The primary outcome was sepsis. Secondary outcomes included all-cause mortality, septic shock, pneumonia, urinary tract infection, and COVID-19. RESULTS: After propensity score matching, 21 035 patients were included in each treatment group. Use of GLP-1RA was associated with a lower risk of sepsis compared with DPP-4i (HR = 0.72; 95% CI, 0.66-0.78). GLP-1RA use was also associated with lower risks of all-cause mortality (HR = 0.65; 95% CI, 0.61-0.70), pneumonia (HR = 0.81; 95% CI, 0.75-0.87), urinary tract infection (HR = 0.83; 95% CI, 0.79-0.88), and COVID-19 (HR = 0.84; 95% CI, 0.77-0.90). The risk of septic shock did not reach Bonferroni-corrected significance level despite being numerically lower (HR = 0.84; 95% CI, 0.73-0.96; P = 0.014). CONCLUSIONS: In patients with CKD and type 2 diabetes mellitus, use of GLP-1RA is associated with lower risks of sepsis, all-cause mortality, pneumonia, urinary tract infection, and COVID-19 compared with DPP-4i, while the risk of septic shock was similar between groups.