Real-World Safety and Clinical Outcomes of SGLT2 Inhibitors in 195 Pediatric Patients

Introduction and Objective: Sodium-glucose cotransport-2 inhibitors (SGLT2i) are increasingly used in pediatric populations despite limited real-world safety data. We evaluated adverse events (AEs) and outcomes among patients prescribed SGLT2i at a large children’s hospital. Methods: We performed a retrospective review of pediatric patients prescribed an SGLT2i from 2019-2025. We abstracted demographics, indication, agent, exposure duration, and prespecified AEs. Patients who never started SGLT2i were included in prescribing counts but excluded from AE incidence calculations. Events attributed to alternate etiologies were not classified as SGLT2i-related AEs. Secondary outcomes included change in HbA1c. Results: Among 195 patients prescribed an SGLT2i, 177 initiated therapy. Of these, 53.7% were male; 44.1% were Hispanic/Latino ethnicity; race was 67.8% White, 22.0% Black, 2.8% Asian, and 4.5% unknown. Indications were cardiac (46.9%), diabetes/metabolic (37.3%), cardio-metabolic (10.7%), renal (3.9%), and unclear/other (1%). Median therapy duration was 19.3 months (interquartile range 11.8-26.0); 78.5% remained on therapy at censoring. AEs included AKI (6.2%), urinary tract infection (5.1%), symptomatic hypoglycemia (1.7%), fracture (1.7%), and mycotic infection (0.6%). All AKI events occurred in the heart failure subgroup. There were 0 cases of SGLT2i-associated deaths, hospitalizations, diabetic ketoacidosis, Fournier’s gangrene, amputation, or volume depletion. HbA1c decreased by 0.62% among all initiators with available follow up data (SD 1.53, n=105), and by 0.79% in the diabetes/metabolic subgroup (SD 1.75; n=76). Conclusion: In this large and diverse real-world pediatric cohort prescribed SGLT2i, we observed low rates of AEs and no new major safety signals, supporting cautious expansion of SGLT2i use in select pediatric populations. Disclosure: S.R. Kelly: None. O. Ginnard: None. R.S. Aguirre: Advisory Panel; Ended; Sanofi. Research Support; Current; Sanofi.