Semaglutide and Tirzepatide in Type 1 Diabetes: Real-World Insulin Deintensification, Cardiovascular Outcomes and Safety Assessment

Semaglutide and tirzepatide are not approved for type 1 diabetes, and their real-world associations with insulin requirements, metabolic outcomes, and safety remain uncertain. Here we analyzed de-identified federated U.S. EHR data, comparing adults with T1D initiating semaglutide (n=1,424) or tirzepatide (n=578) between Jan 1, 2018, and Dec 31, 2025, with 1:1 propensity-score matched T1D controls without GLP-1RA/tirzepatide exposure (n=2,002). At 12 months mean insulin total daily dose (TDD) percent change was −22.0% (median −9.3%) in the semaglutide subcohort and −19.7% (median −17.2%) in the tirzepatide subcohort versus +10.3% (median +0.4%) in matched controls, widening to −27.4% (median −19.4%) and −25.9% (median −31.5%) versus +10.4% (median −1.1%) in controls at 24 months (all P