SGLT2 Inhibitors Are Associated with Lower Risk of Kidney Events and Mortality in Diabetic Ketoacidosis: A Real-World Comparative Cohort Study

Background: SGLT2 inhibitors have revolutionized the management of type 2 diabetes, with proven cardiorenal benefits. However, their role in patients with acute metabolic complications like diabetic ketoacidosis (DKA) remains controversial, largely due to concerns about precipitating or worsening DKA. We aimed to evaluate the short- and long-term outcomes of patients with diabetes and DKA who were on SGLT2 inhibitors compared to those who were not. Methods: We conducted a retrospective comparative cohort analysis using the TriNetX Global Collaborative Network, spanning 148 healthcare organizations. Adult patients (≥18 years) with diabetes and DKA-related ICD-10 codes were included. Two cohorts were constructed: patients exposed to empagliflozin or dapagliflozin (SGLT2 group, n=1,126,214) and those not on any SGLT2 inhibitor (noSGLT2 group, n=9,839,157). Outcomes were assessed at 30 days and 1 year from the index DKA-related event. Primary endpoints included acute kidney injury (AKI), dialysis, ICU admission, mortality (30-day), and incident CKD, ESRD, and 1-year mortality. Results: At 30 days, patients in the SGLT2 group had significantly lower risks of: AKI (4.4% vs 6.0%, RR: 0.74 [95% CI: 0.73–0.74]), Dialysis (0.2% vs 0.7%, RR: 0.27), ICU admission (0.02% vs 0.05%, RR: 0.37), and mortality (0.6% vs 1.4%, RR: 0.47). At 1 year, the SGLT2 group continued to show benefit with: Lower all-cause mortality (2.8% vs 4.0%, RR: 0.70 [95% CI: 0.69–0.70]), Lower incident CKD (8.1% vs 10.7%, RR: 0.76), and lower ESRD rates (0.6% vs 2.1%, RR: 0.30). All comparisons were statistically significant (p<0.001). Survival analysis via Kaplan-Meier curves mirrored these findings, with higher survival probabilities and lower event incidence in the SGLT2 group across all endpoints. Conclusion: In this large, real-world cohort, use of SGLT2 inhibitors in patients with diabetes and DKA was associated with significantly better short- and long-term renal and survival outcomes. These findings challenge the conventional caution surrounding SGLT2 use in the setting of DKA and support further investigation into their safety and potential protective effects in acute metabolic decompensation.