Diabetes medications and associations with Covid-19 outcomes in the N3C database: A national retrospective cohort study

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  • Bramante, C.T.
    • Other Affiliation: University of Minnesota Medical School
  • Johnson, S.G.
    • Other Affiliation: University of Minnesota Medical School
  • Garcia, V.
    • Other Affiliation: Stony Brook University Hospital
  • Evans, M.D.
    • Other Affiliation: University of Minnesota Medical School
  • Harper, J.
    • Other Affiliation: Owl HealthWorks
  • Wilkins, K.J.
    • Other Affiliation: National Institute of Diabetes and Digestive and Kidney Disease
  • Huling, J.D.
    • Other Affiliation: University of Minnesota School of Public Health
  • Mehta, H.
    • Other Affiliation: Johns Hopkins School of Public Health
  • Alexander, C.
    • Other Affiliation: Johns Hopkins School of Public Health
  • Tronieri, J.
    • Other Affiliation: University of Pennsylvania
  • Hong, S.
    • Other Affiliation: Johns Hopkins School of Public Health
  • Kahkoska, A.
    • Affiliation: Gillings School of Global Public Health, Department of Nutrition
  • Alamgir, J.
    • Other Affiliation: ARIScience
  • Koraishy, F.
    • Other Affiliation: Stony Brook University Hospital
  • Hartman, K.
    • Other Affiliation: University of Minnesota Medical School
  • Yang, K.
    • Other Affiliation: University of Minnesota School of Public Health
  • Abrahamsen, T.
    • Other Affiliation: Novo Nordisk
  • Stürmer, T.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Buse, J.B.
    • Affiliation: School of Medicine, Department of Medicine
  • N3C core authors
Abstract
  • Background While vaccination is the most important way to combat the SARS-CoV-2 pandemic, there may still be a need for early outpatient treatment that is safe, inexpensive, and currently widely available in parts of the world that do not have access to the vaccine. There are in-silico, in-vitro, and in-tissue data suggesting that metformin inhibits the viral life cycle, as well as observational data suggesting that metformin use before infection with SARS-CoV2 is associated with less severe COVID-19. Previous observational analyses from single-center cohorts have been limited by size. Methods Conducted a retrospective cohort analysis in adults with type 2 diabetes (T2DM) for associations between metformin use and COVID-19 outcomes with an active comparator design of prevalent users of therapeutically equivalent diabetes monotherapy: metformin versus dipeptidyl-peptidase-4-inhibitors (DPP4i) and sulfonylureas (SU). This took place in the National COVID Cohort Collaborative (N3C) longitudinal U.S. cohort of adults with +SARS-CoV-2 result between January 1 2020 to June 1 2021. Findings included hospitalization or ventilation or mortality from COVID-19. Back pain was assessed as a negative control outcome. Results 6,626 adults with T2DM and +SARS-CoV-2 from 36 sites. Mean age was 60.7 +/- 12.0 years; 48.7% male; 56.7% White, 21.9% Black, 3.5% Asian, and 16.7% Latinx. Mean BMI was 34.1 +/- 7.8kg/m2. Overall 14.5% of the sample was hospitalized; 1.5% received mechanical ventilation; and 1.8% died. In adjusted outcomes, compared to DPP4i, metformin had non-significant associations with reduced need for ventilation (RR 0.68, 0.32–1.44), and mortality (RR 0.82, 0.41–1.64). Compared to SU, metformin was associated with a lower risk of ventilation (RR 0.5, 95% CI 0.28–0.98, p = 0.044) and mortality (RR 0.56, 95% CI 0.33–0.97, p = 0.037). There was no difference in unadjusted or adjusted results of the negative control. Conclusions There were clinically significant associations between metformin use and less severe COVID-19 compared to SU, but not compared to DPP4i. New-user studies and randomized trials are needed to assess early outpatient treatment and post-exposure prophylaxis with therapeutics that are safe in adults, children, pregnancy and available worldwide.
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Resource type
  • Article
License
  • Attribution 4.0 International
Journal title
  • PLoS ONE
Journal volume
  • 17
Journal issue
  • 11-Nov
Language
  • English
Version
  • Publisher
Funder
  • National Institutes of Health’s National Center for Advancing Translational Sciences (NCATS) N3C Data Enclave (https://covid.cd2h. org) and N3C Attribution & Publication Policy v 1.2-2020-08-25b supported by NCATS (U24 TR002306, KL2TR002492, UL1TR002494, UL1TR002489)
  • National Institute of Digestive, Diabetes, and Kidney diseases (K23DK124654, K23DK116935)
ISSN
  • 1932-6203

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