Patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) have heightened vulnerability to infections and infection-related complications. While SGLT-2 inhibitors are established for cardiorenal protection, their association with infection outcomes in this specific high-risk population has been uncertain. The study sought to evaluate whether initiation of SGLT-2 inhibitors versus DPP-4 inhibitors is associated with differences in severe sepsis, infection-related complications, hospitalization, and mortality.
The analysis was a real-world, active-comparator, new-user cohort study using the U.S. Collaborative Network of TriNetX. The study window for treatment initiation spanned 2018 through 2024. The source reports that adults with CKD and T2D who newly started either an SGLT-2 inhibitor or a DPP-4 inhibitor were eligible for inclusion.
Eligible patients were adults with documented CKD and T2D who initiated therapy with either an SGLT-2 inhibitor or a DPP-4 inhibitor in the defined period. An active-comparator design was used, comparing new users of SGLT-2 inhibitors against new users of DPP-4 inhibitors to reduce confounding by indication.
After applying propensity score matching to balance baseline characteristics, the final matched cohorts comprised 25,049 patients in the SGLT-2 inhibitor group and 25,049 patients in the DPP-4 inhibitor group.
The primary outcome specified in the source was severe sepsis. Prespecified secondary outcomes included septic shock, all-cause mortality, hospitalization, pneumonia, urinary tract infection (UTI), and genital infection. Safety outcomes reported included diabetic ketoacidosis and acidosis. Follow-up was reported for 1 year after treatment initiation.
The source states propensity score matching was applied to balance baseline characteristics between treatment groups. Hazard ratios (HRs) with 95% confidence intervals (CIs) were reported for the primary and secondary outcomes over the 1-year follow-up period. The abstract provides HRs and CIs for the main outcomes but does not specify the exact covariates included in the propensity score model in the abstract text.
During 1 year of follow-up, the incidence of severe sepsis was 2.7% in the SGLT-2 inhibitor group versus 3.3% in the DPP-4 inhibitor group. The reported hazard ratio for severe sepsis with SGLT-2 inhibitor use was 0.81 (95% CI, 0.73–0.90), indicating a statistically significant lower risk compared with DPP-4 inhibitors in this matched cohort.
For several key clinical endpoints the source reports reduced risks associated with SGLT-2 inhibitor initiation:
These hazard ratios indicate lower hazards of septic shock, death, and hospitalization over 1 year among patients initiating SGLT-2 inhibitors versus DPP-4 inhibitors in the matched sample.
The study found decreased risks for infection-related outcomes including:
Conversely, the risk of genital infection was higher with SGLT-2 inhibitors (HR 1.93), consistent with known class-specific adverse events related to genital mycotic infections.
The abstract reports no significant differences between groups for diabetic ketoacidosis or acidosis during the 1-year follow-up. The source does not provide specific event counts or hazard ratios for these outcomes in the abstract.
In this large, propensity score–matched real-world cohort of patients with CKD and T2D, initiation of SGLT-2 inhibitors was associated with lower hazards of severe sepsis, septic shock, pneumonia, UTI, hospitalization, and mortality compared with initiation of DPP-4 inhibitors over 1 year. These associations occurred despite an increased hazard of genital infection with SGLT-2 inhibitors. The authors conclude that these findings support SGLT-2 inhibitors as core therapy in this high-risk population, with potential benefits extending beyond established cardiorenal protection.
The abstract does not detail all study limitations. It reports the study design and statistical approach but does not list limitations or describe residual confounding, measurement of outcomes, adjudication methods, or specifics on covariates used in propensity matching in the abstract text. Details beyond those reported in the abstract were not available in the provided source content.
Among adults with CKD and T2D in this TriNetX-based, propensity-matched cohort, SGLT-2 inhibitor initiation was associated with lower 1-year risks of severe sepsis, several infection-related outcomes, hospitalization, and mortality compared with DPP-4 inhibitor initiation, while genital infection risk was increased. The abstract frames these results as supportive of broader clinical benefits of SGLT-2 inhibitors in this high-risk population.