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Cardiovascular safety of GLP-1 receptor agonists for diabetes patients with high cardiovascular risk: A meta-analysis of cardiovascular outcomes trials

  • Qian Wang
    Affiliations
    Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jing 5 Road, Jinan, Shandong Province 250021, China

    Shandong Clinical Medical Center of Endocrinology and Metabolism, 324 Jing 5 Road, Jinan, Shandong Province 250021, China

    Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, 324 Jing 5 Road, Jinan, Shandong Province 250021, China
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  • Lu Liu
    Affiliations
    Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jing 5 Road, Jinan, Shandong Province 250021, China

    Shandong Clinical Medical Center of Endocrinology and Metabolism, 324 Jing 5 Road, Jinan, Shandong Province 250021, China

    Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, 324 Jing 5 Road, Jinan, Shandong Province 250021, China
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  • Ling Gao
    Affiliations
    Shandong Clinical Medical Center of Endocrinology and Metabolism, 324 Jing 5 Road, Jinan, Shandong Province 250021, China

    Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, 324 Jing 5 Road, Jinan, Shandong Province 250021, China

    Scientific Center, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jing 5 Road, Jinan, Shandong Province 250021, China
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  • Qiu Li
    Correspondence
    Corresponding author at: Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jing 5 Road, Jinan, Shandong Province 250021, China.
    Affiliations
    Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jing 5 Road, Jinan, Shandong Province 250021, China

    Shandong Clinical Medical Center of Endocrinology and Metabolism, 324 Jing 5 Road, Jinan, Shandong Province 250021, China

    Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, 324 Jing 5 Road, Jinan, Shandong Province 250021, China
    Search for articles by this author

      Abstract

      Aim

      To show long-term cardiovascular safety of the GLP-1 receptor agonists for diabetes patients with cardiovascular risk.

      Methods

      For cardiovascular outcomes, the association between treatment and outcomes was estimated using the odds ratio and 95% confidence interval. I2 test was adopted to assess the magnitude of heterogeneity between studies, with values more than 25%, 50%, and 75% defined as low, moderate, or high heterogeneity.

      Results

      We combined data from four cardiovascular outcomes trials and prospectively blinded endpoint adjudication. 4105 cardiovascular events including cardiovascular death, acute MI or stroke experienced during the trials. And the odds ratios of the cardiovascular outcomes were 0.90 (95% CI 0.81, 1.00) for the cardiovascular outcome, 0.93 (95% CI 0.85, 1.02) for nonfatal myocardial infarction, 0.88 (95% CI 0.76, 1.03) for nonfatal stroke, 0.94 (95% CI 0.84, 1.05) for heart failure hospitalization, 0.89 (95% CI 0.63, 1.27) for pancreatitis, 0.98 (95% CI 0.92, 1.05) for any hypoglycemic events, 0.92 (95% CI 0.83, 1.01) for the severe hypoglycemic events, 0.96 (95% CI 0.83, 1.01) for serious adverse events. Significant differences showed in mortality parameters: 0.88 (95% CI 0.81, 0.95) for all-cause mortality, 0.87 (95% CI 0.79, 0.97) for cardiovascular mortality. CV benefits were obtained in the male, black, Asian patients and patients with BMI ≥ 30 kg/m2.

      Conclusion

      Additional GLP-1 receptor agonists treatment did not increase cardiovascular outcomes in diabetes patients with high cardiovascular risk or established cardiovascular disease.

      Keywords

      Abbreviations:

      CV (cardiovascular), CVOT (cardiovascular outcome trial), GLP-1 RA (GLP-1 receptor agonist), HbA1c (hemoglobin A1c), MI (myocardial infarction), CI (confidence interval), OR (odds ratio), DM (diabetes mellitus), BMI (, body mass index), DPP4-Is (dipeptidyl peptidase 4 inhibitors)
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