1222-OR: Sodium-Glucose Cotransporter 2 Inhibitors and Clinical Outcomes in Type 1 Diabetes: A Target Trial Emulation Study

Introduction and Objective: Evidence of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in type 1 diabetes (T1D) is limited to short-term trials with surrogate endpoints. Using real-world data, we aimed to assess long-term clinical outcomes of SGLT2i in T1D. Methods: Using electronic health record data from Optum Labs Data Warehouse, we conducted monthly sequential target trial emulation (SGLT2i initiation vs. other non-insulin glucose-lowering agents except GLP-1RA) between 2013-2024 (138 trials) in 17,850 people with T1D. Primary outcomes were 1) composite of end-stage kidney disease or kidney-related death and 2) hospitalization for heart failure (HHF). Safety outcomes were hospitalization for diabetic ketoacidosis (DKA) and severe hypoglycemia. We used Cox models, adjusting for confounders by propensity score overlap weighting. Results: Among 21,766 person-trials (median follow-up 3.6 years), 3,349 initiated SGLT2i and 18,417 initiated other agents. After weighting, SGLT2i initiation was associated with lower risks of composite kidney outcome (HR, 0.71 95% CI: 0.54-0.95) and HHF (0.80 0.66-0.97, Figure). There was a numerically higher risk of DKA (1.08 0.94-1.24), although this association was not statistically significant. The risk of severe hypoglycemia was lower with SGLT2i (0.78 0.68-0.90). Conclusion: SGLT2i may reduce risks of adverse kidney outcomes and heart failure in T1D but potentially increase the risk of DKA. Disclosure Y. Xu: None. N. Malek: None. A. Chang: Research Support; Current; Novartis AG, Bayer AG. Advisory Panel; Ended; Amgen Inc. Research Support; Current; Boehringer Ingelheim International GmbH, AstraZeneca, Vertex Pharmaceuticals Incorporated. J. Echouffo Tcheugui: None. E. Selvin: Other - In 2025, Dr. Selvin received payment for an educational webinar (content her own) sponsored by Siemens Healthineers and hosted by the Association for Diagnostics Ended; Siemens. M. Grams: Other - Received a grant from the NKF that was funded by Vertex; Ended; Vertex Pharmaceuticals Incorporated. M. Fang: None. J. Shin: Research Support; Current; Bayer AG. Funding NIDDK (R01DK139324)