Introduction and Objective: Evidence for GLP-1RA-associated cardiovascular benefits in type 1 diabetes (T1D) remains scarce. Using a target trial emulation, we assessed the impact of GLP-1RA use on cardiovascular outcomes in a high-risk cohort of adults with T1D and overweight or obesity.Methods: We emulated a target trial using electronic health records from Epic COSMOS database. Adults with T1D and body mass index (BMI) ≥27 kg/m² who newly initiated a GLP-1RA between 2020 and 2024 were compared with eligible nonusers. Participants from the two study arms were sequentially matched by calendar time to align the start of follow-up. High-dimensional propensity score matching with inverse probability weighting was subsequently employed to balance a wide range of baseline characteristics, including demographics, labs, clinical comorbidities, and prior healthcare use. The primary outcome was major adverse cardiovascular events (MACE), defined as myocardial infarction, stroke, or all-cause mortality. Secondary outcomes included heart failure (HF), atrial fibrillation (AF), and peripheral vascular disease (PVD). We conducted per-protocol analysis using Cox proportional hazards models to estimate associations between GLP-1RA use and study outcomes.Results: The final cohort included 23,527 GLP-1RA users and 102,676 matched nonusers (mean age 52.1 years; 55.9% female). The majority (81.1%) were commercially insured, and 21% had pre-existing CVD at baseline. GLP-1RA use was associated with a 31% lower risk of MACE (HR 0.69, 95% CI 0.63-0.76; p<0.001). Significant risk reductions were also observed for AF (HR 0.82, 95% CI 0.70-0.96) and HF (HR 0.83, 95% CI 0.74-0.94). No significant associations were found for PVD (HR 1.04, 95% CI 0.94-1.16).Conclusion: Our results support the clinical integration of GLP-1RAs as a targeted strategy to reduce macrovascular complications in high-risk T1D patients, paralleling established standards in type 2 diabetes care.
Y. Shao: None. P. Li: None. G. Davis: Research Support; Current; Insulet Corporation, Sequel Med Tech. E. Mitchell: None. C.A. Ackeifi: None. Q. Xue: None. F.J. Pasquel: Research Support; Current; Dexcom, Inc., Insulet Corporation, Ideal Medical Technologies. Research Support; Ended; Novo Nordisk, Tandem Diabetes Care, Inc. Consultant; Ended; Insulet Corporation. H. Shao: None.
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