Metformin Use Is Associated With Reduced Mortality in a Diverse Population With COVID-19 and Diabetes

  1. Andrew B. Crouse
  2. Tiffany Grimes
  3. Peng Li
  4. Matthew Might
  5. Fernando Ovalle
  6. Anath Shalev

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Abstract

Coronavirus disease-2019 (COVID-19) is a growing pandemic with an increasing death toll that has been linked to various comorbidities as well as racial disparity. However, the specific characteristics of these at-risk populations are still not known and approaches to lower mortality are lacking.

Methods

We conducted a retrospective electronic health record data analysis of 25,326 subjects tested for COVID-19 between 2/25/20 and 6/22/20 at the University of Alabama at Birmingham Hospital, a tertiary health care center in the racially diverse Southern U.S. The primary outcome was mortality in COVID-19-positive subjects and the association with subject characteristics and comorbidities was analyzed using simple and multiple linear logistic regression.

Results

The odds ratio of contracting COVID-19 was disproportionately high in Blacks/African-Americans (OR 2.6; 95% CI 2.19–3.10; p<0.0001) and in subjects with obesity (OR 1.93; 95% CI 1.64–2.28; p<0.0001), hypertension (OR 2.46; 95% CI 2.07–2.93; p<0.0001), and diabetes (OR 2.11; 95% CI 1.78–2.48; p<0.0001). Diabetes was also associated with a dramatic increase in mortality (OR 3.62; 95% CI 2.11–6.2; p<0.0001) and emerged as an independent risk factor in this diverse population even after correcting for age, race, sex, obesity, and hypertension. Interestingly, we found that metformin treatment prior to diagnosis of COVID-19 was independently associated with a significant reduction in mortality in subjects with diabetes and COVID-19 (OR 0.33; 95% CI 0.13–0.84; p=0.0210).

Conclusion

Thus, these results suggest that while diabetes is an independent risk factor for COVID-19-related mortality, this risk is dramatically reduced in subjects taking metformin prior to diagnosis of COVID-19, raising the possibility that metformin may provide a protective approach in this high risk population.

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  1. ScreenIT

    SciScore for 10.1101/2020.07.29.20164020: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Study design and participants: We conducted a retrospective analysis of de-identified electronic health record data from subjects consecutively tested for COVID-19 between February 25, 2020 and June 22, 2020 at UAB (Institutional Review Board protocol E160105006).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    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:
    Limitations of the study include the size that did not allow for any separate analyses of additional subgroups such as T1D or subjects on other anti-diabetic drugs besides metformin. On the other hand, the diverse community comprising a large proportion of African-American men and women represents a unique feature of our study. Most strikingly, we found that metformin use prior to the diagnosis of COVID-19 was associated with a ~3-fold decrease in mortality and significantly lower unadjusted and adjusted odds ratios in subjects with diabetes. Of note, this effect remained even after correcting for age, sex, race, obesity and hypertension or chronic kidney disease and heart failure. Interestingly and in alignment with this finding, an early report from Wuhan, China also suggested that metformin was associated with decreased mortality in hospitalized COVID-19 patients with diabetes in (13). Metformin was also found to be associated with reduced risk of early death in the French CORONADO study (6) and most recently, it was suggested to be associated with decreased mortality in women with COVID-19 based on a UnitedHealth data analysis (14). The fact that such similar results were obtained in different populations from around the world suggests that the observed reduction in mortality risk, associated with metformin use in subjects with T2D and COVID-19, might be generalizable. Furthermore, these findings underline the importance of following general diabetes treatment and prevent...

    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.

  2. Version published to 10.3389/fendo.2020.600439
  3. ScreenIT

    SciScore for 10.1101/2020.07.29.20164020: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementMETHODS Study design and participants We conducted a retrospective analysis of de-identified electronic health record data from subjects consecutively tested for COVID-19 between February 25, 2020 and June 22, 2020 at UAB (Institutional Review Board protocol E160105006).Randomizationnot detected.Blindingnot detected.Power Analysisnot detected.Sex as a biological variable93% of deaths occurred in subjects over the age of 50 and male sex as well as hypertension were associated with a significantly elevated risk of death as assessed by bivariate logistic regression analysis (Table 2).

    Table 2: Resources

    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 10.1101/2020.07.29.20164020v1 on medRxiv