Comparative risk of infections with GLP-1 receptor agonists versus SGLT2 inhibitors in patients with advanced chronic kidney disease and type 2 diabetes.

AIMS: To compare the risk of infections between GLP-1 receptor agonists (GLP-1 RAs) and SGLT2 inhibitors (SGLT2i) in patients with type 2 diabetes mellitus (T2DM) and advanced chronic kidney disease (CKD).

METHODS

Using the TriNetX U.S. Collaborative Network, we conducted a retrospective cohort study of adults with T2DM and eGFR ≤ 45 mL/min/1.73 m2 from 2016 to 2023. After 1:1 propensity score matching, 22,393 new users of GLP-1 RAs and SGLT2i were compared. Infection outcomes were analyzed over a 4-year follow-up using Cox models and Kaplan-Meier analysis.

RESULTS

GLP-1 RA use was associated with a modest increase in overall infection risk compared to SGLT2i (HR 1.04, 95% CI: 1.00-1.07; P = 0.044). Notably, higher risks were observed for biliary tract infections (HR 1.37), catheter-related infections (HR 1.34), and infective endocarditis (HR 1.31). No differences were seen in pneumonia, sepsis, or urinary tract infections. Subgroup analyses showed consistent trends across age, sex, BMI, and cardiovascular status.

CONCLUSIONS

In patients with T2DM and advanced CKD, GLP-1 RAs were associated with higher risks of select infections compared to SGLT2i. These findings highlight the need for careful infection monitoring in this vulnerable population.