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

Publication date: Aug 07, 2026

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. 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. 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). 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.

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