Chronic Treatment with SGLT-2 Inhibitors is Associated with ICU Admission and Disease Severity in Patients with Diabetic Ketoacidosis: A Propensity Score–Matched Cohort Study

Abstract Introduction: SGLT-2 inhibitors (SGLT-2i) are linked to a higher risk of diabetic ketoacidosis (DKA). However, it is still unclear whether the severity of SGLT-2i associated DKA is higher. Methods: This is a retrospective cohort study with patients admitted for DKA at a tertiary hospital (2013-2024). Patients were matched by propensity score for age, sex, diabetes duration, type, and ischemic heart disease. ICU admission risk and clinical severity were compared between SGLT-2i users and controls. Results: The matched sample included 105 subjects (35 SGLT-2i users, 70 controls). The average age was 63.1±15.4 years, and 40 (38.1%) patients were women. ICU admission was higher in the treatment group (65.7% versus 24.6%, p<0.001). A conditional logistic regression showed higher risk of ICU admission in the treatment group (odds ratio 12.7, 95% confidence interval 1.9 - 84.3, p=0.009) after adjusting for confounding factors. The treatment group exhibited less favorable blood gas results (pH 7.10±0.17 vs 7.18±0.16, p=0.024) and shorter symptom duration (2 [1-3] vs 3 [2-7] days, p<0.002). No significant differences were found in diabetes type, ketonemia, creatinine, or DKA precipitating factors. Conclusion: DKA in patients with diabetes treated with SGLT-2i is associated with more severe acidosis with quicker onset, leading to higher risk of ICU admission compared to patients not receiving this treatment. We recommend temporary discontinuation of SGLT-2i during any acute event until resolution, regardless of diabetes type or the patient's glycemic control.