Association between SGLT2 inhibitor use and risk of sepsis-induced cardiomyopathy in patients with type 2 diabetes: a propensity-matched cohort study

AIM: Sepsis-induced cardiomyopathy (SICM) is a transient cardiac dysfunction that occurs in a substantial proportion of patients with sepsis and is associated with poor prognosis. However, preventive strategies remain limited. This study aimed to assess whether baseline use of sodium-glucose co-transporter 2 inhibitors (SGLT2is) compared to dipeptidyl peptidase-4 inhibitors (DPP4is) is associated with a reduced risk of SICM in patients with type 2 diabetes mellitus (T2D) and sepsis. METHODS: Using the TriNetX global health research network, we conducted a retrospective cohort study including adult patients with T2D and infection who were prescribed either SGLT2is or DPP4is within three months before infection. Propensity score matching (PSM) was applied to balance baseline characteristics. The primary outcome was SICM within 30 days; secondary outcomes included 1-year all-cause mortality, hospitalization, and major adverse cardiovascular events (MACEs). RESULTS: After 1:1 PSM for demographics, comorbidities, and medications, 73,069 patients were included in each group. SGLT2is use was associated with a significantly lower risk of SICM (hazard ratio [HR], 0.78; 95% CI, 0.71-0.86), all-cause mortality (HR, 0.58; 95% CI, 0.55-0.62), hospitalization (HR, 0.83; 95% CI, 0.79-0.87), and MACEs (HR, 0.86; 95% CI, 0.80-0.93), all P < .001, compared to DPP4is therapy. Subgroup analyses and negative control outcomes supported the robustness of the findings. CONCLUSIONS: Among patients with T2D and sepsis, SGLT2is were associated with a lower risk of SICM and improved long-term cardiovascular outcomes, compared to DPP4is therapy. These results support further prospective studies to validate the role of SGLT2is in preventing SICM.