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Is the steady-state concentration, duration of action, or molecular weight of GLP-1RA associated with cardiovascular and renal outcomes in type 2 diabetes?

  • Author Footnotes
    1 Shuzhen Bai and Chu Lin contributed equally to this manuscript.
    Shuzhen Bai
    Footnotes
    1 Shuzhen Bai and Chu Lin contributed equally to this manuscript.
    Affiliations
    Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China
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  • Author Footnotes
    1 Shuzhen Bai and Chu Lin contributed equally to this manuscript.
    Chu Lin
    Footnotes
    1 Shuzhen Bai and Chu Lin contributed equally to this manuscript.
    Affiliations
    Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China
    Search for articles by this author
  • Ruoyang Jiao
    Affiliations
    Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China
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  • Xiaoling Cai
    Correspondence
    Corresponding author at: Department of Endocrinology and Metabolism, Peking University People's Hospital, No.11 Xizhimen South Street, Xicheng District, Beijing, China, 100044.
    Affiliations
    Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China
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  • Suiyuan Hu
    Affiliations
    Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China
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  • Fang Lv
    Affiliations
    Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China
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  • Wenjia Yang
    Affiliations
    Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China
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  • Xingyun Zhu
    Affiliations
    Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China
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  • Linong Ji
    Correspondence
    Corresponding author at: Department of Endocrinology and Metabolism, Peking University People's Hospital, No.11 Xizhimen South Street, Xicheng District, Beijing, China, 100044.
    Affiliations
    Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China
    Search for articles by this author
  • Author Footnotes
    1 Shuzhen Bai and Chu Lin contributed equally to this manuscript.
Published:January 09, 2023DOI:https://doi.org/10.1016/j.ejim.2023.01.008

      Highlights

      • Disparities were found in the cardiorenal outcomes among different GLP-1RAs.
      • GLP-1RAs with high concentration was associated with less cardiorenal events.
      • Long acting GLP-1RAs was associated more improved cardiovascular outcomes.
      • The molecular weight of GLP-1RAs did not influence the cardiorenal outcomes.

      Abstract

      Importance

      Disparities were found in the cardiovascular and renal outcomes among different glucagon-like peptide 1 receptor agonist (GLP-1RA) subtypes. However, whether the characteristics of GLP-1RA itself are associated with these disparities remains unclear.

      Objective

      To assess the association between the steady-state concentration, duration of action, or molecular weight of GLP-1RA and the risks of cardiovascular and renal outcomes in patients with type 2 diabetes (T2D).

      Data Sources

      PubMed, MEDLINE, EMBASE, Cochrane and Clinicaltrial.gov from inception to April 2022.

      Study Selection

      Randomized controlled trials (RCTs) investigating GLP-1RAs in patients with T2D were included.

      Data Extraction And Synthesis

      Literature screening and data extraction were performed independently by 2 researchers. The outcomes were computed as odds ratio (OR) and its 95% confidence interval (CI). Subgroup analyses were conducted according to steady-state concentration, duration of action and molecular weight of GLP-1RAs.

      Main Outcomes and Measures

      Primary outcomes were major adverse cardiovascular events (MACE), composite renal outcome and all-cause mortality.

      Results

      In all, 61 RCTs were included. When compared with non-GLP-1RA agents, GLP-1RAs with high steady-state concentration were associated with greater risk reduction in MACE (p for subgroup difference = 0.01) and the composite renal outcome (p for subgroup difference = 0.008) in patients with T2D. Greater risk reductions in MACE between GLP-1RA users versus non-GLP-RA users were observed in long acting stratum when compared with short acting stratum (p for subgroup difference = 0.04) in patients with T2D. The molecular weight of GLP-1RAs was not associated with the risk of cardiovascular and renal outcomes.

      Conclusions and Relevance

      GLP-1RAs with high steady-state concentrations might be associated with greater risk reductions in cardiovascular and renal outcomes in patients with T2D. Long acting GLP-1RAs might outperform short acting ones in reducing the risk of cardiovascular outcomes. These findings provided new insights for guiding the clinical applications of GLP-1RAs in patients with T2D.

      Keywords

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