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Effect of Glucagon-like Peptide-1 Receptor Agonists on Lipid Profiles Among Type 2 Diabetes: A Systematic Review and Network Meta-analysis

  • Author Footnotes
    ⁎ These authors contributed equally to this work.
    Feng Sun
    Footnotes
    ⁎ These authors contributed equally to this work.
    Affiliations
    Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China

    Department of Preventive Medicine, College of Medicine, Shihezi University, Shihezi, China
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  • Author Footnotes
    ⁎ These authors contributed equally to this work.
    Shanshan Wu
    Footnotes
    ⁎ These authors contributed equally to this work.
    Affiliations
    Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China
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  • Jing Wang
    Affiliations
    Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China
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  • Shuxia Guo
    Affiliations
    Department of Preventive Medicine, College of Medicine, Shihezi University, Shihezi, China
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  • Sanbao Chai
    Affiliations
    Department of Physiology, Capital Medical University, Beijing, China
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  • Zhirong Yang
    Affiliations
    Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China

    Shantou-Oxford Clinical Research Unit, Shantou University Medical College, Guangdong, China
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  • Lishi Li
    Affiliations
    Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China

    Department of Statistics, Graduate School of Arts and Sciences, Columbia University, New York, New York
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  • Yuan Zhang
    Affiliations
    Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China
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  • Linong Ji
    Affiliations
    Department of Endocrinology and Metabolism, People’s Hospital, Peking University, Beijing, China
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  • Siyan Zhan
    Correspondence
    Address correspondence to: Siyan Zhan, PhD, Department of Epidemiology and Bio-statistics, School of Public Health, Peking University Health Science Centre, 38 Xueyuan Road, Haidian District, Beijing, China, 100191
    Affiliations
    Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China
    Search for articles by this author
  • Author Footnotes
    ⁎ These authors contributed equally to this work.

      Abstract

      Purpose

      The goal of this study was to assess the effect of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on lipid profiles in patients with type 2 diabetes.

      Methods

      The MEDLINE, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched from inception through October 31, 2013. Randomized controlled trials with available data were selected if they compared GLP-1 RAs with placebo and traditional antidiabetic drugs with a duration ≥8 weeks. The weighted mean difference for changes in lipid profiles was estimated by using the random effects model, and a network meta-analysis was performed to supplement direct comparisons.

      Findings

      Thirty-five trials with 13 treatments were included in the analysis. GLP-1 RAs decreased HDL-C with a range of –0.06 mmol/L (95% CI, –0.11 to –0.01) to –0.13 mmol/L (95% CI, –0.17 to –0.10) compared with thiazolidinediones, whereas thiazolidinediones were associated with a significant increase in HDL-C compared with placebo (0.09 mmol/L [95% CI, 0.06 to 0.12]). A significant reduction in LDL-C was detected for all GLP-1 RAs versus placebo (range, –0.08 to –0.16 mmol/L), insulin (range, –0.10 to –0.19 mmol/L), and thiazolidinediones (range, –0.16 to –0.24 mmol/L). Exenatide, liraglutide 1.8 mg once daily, and taspoglutide decreased total cholesterol with a range of –0.16 mmol/L (95% CI, –0.26 to –0.06) to –0.27 mmol/L (95% CI, –0.41 to –0.12) versus placebo and thiazolidinediones (range, –0.26 to –0.37 mmol/L). The decreased effect was more evident in exenatide long-acting release and liraglutide 1.8 mg once daily. A significant reduction in triglyceride levels was observed with liraglutide 1.8 mg once daily (–0.30 mmol/L [95% CI, –0.49 to –0.11]) and taspoglutide 20 mg once weekly (–0.17 mmol/L [95% CI, –0.31 to –0.01]) versus placebo.

      Implications

      GLP-1 RAs were associated with modest reductions in LDL-C, total cholesterol, and triglycerides but no significant improvement in HDL-C. Further evidence is needed to determine if improvements in lipid profiles might translate into reductions in cardiovascular outcomes.

      Key words

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