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GLP-1 receptor agonists in diabetes for stroke prevention: a systematic review and meta-analysis

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Abstract

Background

Randomized controlled clinical trials (RCT) have demonstrated varied efficacy of glucagon-like peptide-1 receptor (GLP-1R) agonists for cardiovascular outcomes. We sought to evaluate the efficacy and safety of GLP-1R agonists among patients with Type 2 diabetes mellitus (DM) for stroke prevention.

Methods

We conducted a systematic review and meta-analysis of RCTs reporting the following outcomes among patients with Type 2 DM treated with GLP-1R agonists (vs. placebo): nonfatal or fatal strokes, all-cause or cardiovascular mortality, myocardial infarction (MI) and major adverse cardiovascular events (MACE). The protocol of our systematic review and meta-analysis was registered to the PROSPERO database. We pooled odds ratios (OR) using random-effect models, and assessed the heterogeneity using Cochran Q and I2 statistics.

Results

We identified 8 RCTs, comprising 56,251 patients. In comparison to placebo, GLP-1R agonists reduced nonfatal strokes (OR 0.84; 95% CI 0.76–0.94, p = 0.002; I2 = 0%) and all strokes (OR 0.84; 95% CI 0.75–0.93, p = 0.001; I2 = 0%) by 16%. Overall, GLP-1R agonists reduced MACE by 13% (OR 0.87; 95% CI 0.81–0.94, p = 0.0003; I2 = 42%), cardiovascular mortality by 12% (OR 0.88; 95% CI 0.81–0.95; p = 0.002; I2 = 0%) and all-cause mortality by 12% (OR 0.88; 95% CI 0.82–0.95, p = 0.0007; I2 = 15%). Additional analyses demonstrated that GLP-1R agonists reduced the risk of incident MACE (OR 0.86; 95% CI 0.80–0.92; p < 0.0001; I2 = 0%) among patients with prior history of MI or nonfatal strokes.

Conclusions

Among patients with type 2 DM, GLP-1R agonists are beneficial for primary stroke, MACE, and cardiovascular mortality prevention. Further RCTs are needed to evaluate their role for secondary stroke prevention.

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Funding

The study received no specific grant or funding.

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Authors and Affiliations

  1. Department of Neurology, Allegheny Health Network, Pittsburgh, PA, USA

    Konark Malhotra

  2. Division of Neurology, McMaster University/Population Health Research Institute, Hamilton, Canada

    Aristeidis H. Katsanos

  3. Second Department of Internal Medicine, Research Institute and Diabetes Center, National and Kapodistrian University of Athens, “Attikon” University Hospital, Athens, Greece

    Vaia Lambadiari

  4. Department of Neurology, University of Tennessee Health Science Center, Memphis, TN, USA

    Nitin Goyal, Andrei V. Alexandrov & Georgios Tsivgoulis

  5. Second Department of Neurology, “Attikon” University Hospital, National and Kapodistrian University of Athens, Athens, Greece

    Lina Palaiodimou & Georgios Tsivgoulis

  6. First Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece

    Maria Kosmidou

  7. Department of Neurology, St. Josef-Hospital, Ruhr University Bochum, Bochum, Germany

    Christos Krogias

Authors
  1. Konark Malhotra
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  2. Aristeidis H. Katsanos
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  3. Vaia Lambadiari
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  4. Nitin Goyal
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  5. Lina Palaiodimou
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  6. Maria Kosmidou
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  7. Christos Krogias
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  8. Andrei V. Alexandrov
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  9. Georgios Tsivgoulis
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Contributions

KM: study concept and design, acquisition of data, analysis and interpretation, critical revision of the manuscript for important intellectual content. AHK: acquisition of data & critical revision of the manuscript for important intellectual content. VL: critical revision of the manuscript for important intellectual content. NG: critical revision of the manuscript for important intellectual content. LP: critical revision of the manuscript for important intellectual content. MK: critical revision of the manuscript for important intellectual content. CK: critical revision of the manuscript for important intellectual content. AVA: critical revision of the manuscript for important intellectual content. GT: study concept and design, critical revision of the manuscript for important intellectual content.

Corresponding author

Correspondence to Konark Malhotra.

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The manuscript provides aggregate data that is publically available from published studies. It does not contain individual patient data, and therefore approval from the ethics committee or patient consent was not required.

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Malhotra, K., Katsanos, A.H., Lambadiari, V. et al. GLP-1 receptor agonists in diabetes for stroke prevention: a systematic review and meta-analysis. J Neurol 267, 2117–2122 (2020). https://doi.org/10.1007/s00415-020-09813-4

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  • DOI: https://doi.org/10.1007/s00415-020-09813-4

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