Abstract Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are increasingly used for their cardiovascular and renal benefits beyond glucose control. As their use expands, questions arise about their effects during acute illnesses such as sepsis. Previous real-world studies have shown a reduced incidence of pneumonia and respiratory complications in ambulatory SGLT2i users; however, limited data exist on outcomes once sepsis develops. This study evaluated whether prior SGLT2i use influences major outcomes in patients with sepsis. Methodology A retrospective cohort study was conducted using the TriNetX US Collaborative Network. Adults aged 18-80 years with heart failure with reduced ejection fraction (LVEF ≤50%) who developed sepsis between November 1, 2019, and November 1, 2024, were included. Patients were categorized by exposure to SGLT2i: those with use within 3 months before or on the day of sepsis formed the SGLT2i cohort, while the non-SGLT2i cohort had no exposure. Outcomes within 30 days of the index sepsis event were evaluated. Propensity score matching (1:1) was applied to balance covariates. Kaplan-Meier and log-rank tests compared outcomes, with hazard ratios (HR) and 95% confidence intervals (CI) reported; p 0.05 was considered significant. Results In this real-world cohort of septic patients, prior SGLT2i use was associated with favorable respiratory outcomes and comparable hemodynamic and mortality profiles. The HR for all-cause mortality was 1.115 (95% CI 0.958-1.297; p = 0.158), showing no significant difference between SGLT2i users and non-users. Similarly, the need for pressor support (HR 1.027; 95% CI 0.945-1.116; p = 0.531) and circulatory support/ECMO (HR 0.629; 95% CI 0.33-1.12; p = 0.05) did not differ significantly. Non-users had a higher risk of intubation and ventilator-associated pneumonia (VAP), with adjusted HRs of 1.336 (95% CI 1.083-1.648; p = 0.007) and 1.908 (95% CI 1.113-3.279; p = 0.017), respectively. The need for non-invasive ventilation was lower among SGLT2i users (HR 0.883; 95% CI 0.723-1.079; p = 0.232 for 24 hours; HR 0.766; 95% CI 0.513-1.145; p = 0.193 for 24 hours), though not statistically significant. Discussion and Conclusions Prior SGLT2i use may reduce the risk of invasive respiratory interventions and VAP in sepsis without adversely affecting survival or hemodynamic stability. These findings align with prior studies suggesting respiratory benefits of SGLT2i therapy, potentially via improved pulmonary hemodynamics, metabolic modulation, or attenuation of inflammatory injury. Overall, SGLT2i therapy appears safe in patients who later develop sepsis, though prospective studies are warranted to confirm these associations This abstract is funded by: None
Bashir et al. (Fri,) studied this question.
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