GLP-1 RA initiation versus metformin and risk of cardiomyopathy in patients with cancer and diabetes treated with chemotherapy, radiation, or immunotherapy: a target trial emulation.
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AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1 RA) have demonstrated cardioprotective effects; however, their association with cardiomyopathy remains unclear among patients with cancer and type 2 diabetes mellitus (T2D) treated with chemotherapy, radiation, or immunotherapy. We evaluated whether GLP-1 RA initiation reduces cardiomyopathy risk compared with metformin. METHODS: We conducted a retrospective cohort study using a target trial emulation framework within a large global electronic health record database. Adults aged 18-75 years with cancer and T2D, and prior exposure to chemotherapy, radiation, or immunotherapy were included. Treatment strategies were initiation of GLP-1 RA or metformin between January 2006 and July 2024. The primary outcome was incident cardiomyopathy. A 1:1 propensity score-matched cohort was created, and risk differences (RD) and hazard ratios (HR) were estimated. RESULTS: Among 10,382 matched patients, cardiomyopathy risk at 18.5 years was lower among GLP-1 RA initiators than metformin initiators (0.31% vs 0.94%; RD - 0.64%, 95% CI - 0.90 to - 0.30; HR 0.43, 95% CI 0.24-0.76). Results were consistent across high-risk subgroups. CONCLUSIONS: GLP-1 RA initiation was associated with a lower risk of cardiomyopathy compared with metformin among patients with cancer and T2D, supporting a potential role for GLP-1 RA in cardio-oncology prevention strategies.