DPP-4 Inhibitors and Respiratory Infection: A Systematic Review and Meta-analysis of the Cardiovascular Outcomes Trials

  1. Guillaume Grenet
  2. Samia Mekhaldi
  3. Sabine Mainbourg
  4. Marine Auffret
  5. Catherine Cornu
  6. Jean-Luc Cracowski
  7. François Gueyffier
  8. Jean-Christophe Lega
  9. Michel Cucherat

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Abstract

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  1. Version published to 10.2337/dc20-2018
  2. ScreenIT

    SciScore for 10.1101/2020.07.28.20163386: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableWe excluded specific populations as children and pregnant women.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    26 We updated the searche for CVOTs assessing a DPP4 inhibitor versus a placebo, in type 2 diabetes mellitus, in PubMed and CENTRAL, up to January 27, 2020.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    In line with our previous meta-analysis,26 we used the Cochrane Collaboration’s tool for assessing risk of bias in RCTs.
    Cochrane Collaboration’s
    suggested: None

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Our study has strengths and limitations. To the best of our knowledge, our study is the most comprehensive meta-analysis of large CVOTs assessing the risk of respiratory infection with DPP4 inhibitors, in patients with type 2 diabetes, before the COVID-19 pandemic. We even found one early-terminated CVOT not included in the last meta-analysis of glucose lowering drugs.16 We summarized the information from five placebo-controlled CVOTs, including 47 714 patients. We firstly focused on placebo-controlled CVOTs, to avoid both the pitfalls of small study effect and of heterogeneous comparators. This could lead to a loss of information. However, the non-CVOTs have a relatively small sample size and time of follow up compared to the CVOTs. Thus, we expected the CVOTs to drive the main number of events. A previous meta-analysis of non-CVOTs DPP4 inhibitors studies provided treatment effect estimates on cardiovascular outcomes eventually disproved by CVOT.35 To limit the risk of a loss of information with our methodological choice, we added a sensitivity analysis to verify the treatment effect estimation using both active-controlled CVOTs and non-CVOTs studies, which showed the robustness of our primary analysis. The placebo-controlled CVOTs reported more events (4 369) than the previous meta-analysis of non-CVOTs studies (3 904).5 Integrating the placebo-controlled CVOTs, the active-controlled CVOT and the non-CVOTs studies, we provide a very precise estimation using an overall samp...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. ScreenIT

    SciScore for 10.1101/2020.07.28.20163386: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementEthics approval and consent to participate: not applicable.RandomizationSince the last meta-analyses assessing the risk of infections with DPP4 inhibitors, powerful cardiovascular outcomes randomized trials (CVOTs) became available.Blindingnot detected.Power AnalysisFinally, we provide an estimation with a lower risk of bias and a greater statistical power compared to the previous pharmacovigilance studies.Sex as a biological variableWe excluded specific populations as children and pregnant women.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    We searched for published and unpublished CVOTs in Medline, the Cochrane Central Register of Controlled
    Medline
    suggested: (MEDLINE, SCR_002185)
    26 We updated the searche for CVOTs assessing a DPP4 inhibitor versus a placebo, in type 2 diabetes mellitus, in PubMed and CENTRAL, up to January 27, 2020.
    PubMed
    suggested: (PubMed, SCR_004846)
    In line with our previous meta-analysis,26 we used the Cochrane Collaboration’s tool for assessing risk of bias in RCTs.
    Cochrane Collaboration’s
    suggested: None

    Data from additional tools added to each annotation on a weekly basis.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.

  4. Version published to 10.1101/2020.07.28.20163386v1 on medRxiv