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Effectiveness of tirzepatide in patients with HFpEF using a target trial emulation retrospective cohort study

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  • Yu-Min Lin

    (Chiali)

  • Kuang-Ming Liao

    (Chiali
    Min-Hwei Junior College of Health Care Management)

  • Tsung Yu

    (National Cheng Kung University)

  • Jheng-Yan Wu

    (National Cheng Kung University
    Chi Mei Medical Center)

  • Chih-Cheng Lai

    (Chi Mei Medical Center
    National Sun Yat-sen University)

Abstract

Tirzepatide, a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, has shown promise in improving metabolic and cardiovascular profiles in patients with obesity. However, its potential benefits in patients with heart failure with preserved ejection fraction (HFpEF) remain unclear. We conducted a real-world, retrospective cohort study using the TriNetX global database. A total of 14,154 patients with HFpEF were included after 1:1 propensity score matching. Tirzepatide use was associated with significantly lower risks of the primary composite outcome of heart failure exacerbation and all-cause mortality (HR 0.52), as well as reductions in major adverse cardiovascular events (HR 0.64) and major adverse kidney events (HR 0.44). Subgroup analyses demonstrated consistent benefits across different strata. Sensitivity analyses using alternative exposure definitions confirmed the robustness of the findings. These results support the potential clinical utility of tirzepatide in HFpEF management and warrant further investigation in randomized controlled trials.

Suggested Citation

  • Yu-Min Lin & Kuang-Ming Liao & Tsung Yu & Jheng-Yan Wu & Chih-Cheng Lai, 2025. "Effectiveness of tirzepatide in patients with HFpEF using a target trial emulation retrospective cohort study," Nature Communications, Nature, vol. 16(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59616-2
    DOI: 10.1038/s41467-025-59616-2
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    1. Jia-Yuh Sheu & Li-Yang Chang & Jui-Yi Chen & Heng-Chih Pan & Chi-Shin Tseng & Jeff S. Chueh & Vin-Cent Wu, 2024. "The outcomes of SGLT-2 inhibitor utilization in diabetic kidney transplant recipients," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
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