ArticlePloS one2022
Diabetes medications and associations with Covid-19 outcomes in the N3C database: A national retrospective cohort study.
Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 7 citations in OpenAlex.
- Metformin for Treatment of Acute COVID-19: Systematic Review of Clinical Trial Data Against SARS-CoV-2.Diabetes care · 2023Pooled it
- Metformin and Severe Post-COVID-19 Outcomes Among Individuals with Diabetes Mellitus.medRxiv : the preprint server for health sciences · 2026Article
- GLP Medications and Severe Post-COVID-19 Outcomes Among Individuals with Type 2 Diabetes Mellitus.medRxiv : the preprint server for health sciences · 2026Article
- Clinical Outcomes with the Use of Dipeptidyl Peptidase-4 (DPP-4) Inhibitor Among Patients with Diabetes Mellitus and COVID-19: A Systematic Review of Observational Studies.Journal of clinical medicine · 2026Review
- The Role of Viral Infections in the Immunopathogenesis of Type 1 Diabetes Mellitus: A Narrative Review.Biology · 2025Review
- Increasing the Utility of Real-World Data to Inform Public Health Decision Making Through a US-based Private-Public Partnership: 10 Lessons Learned from a Principled Approach to Rapid Pandemic RWE Generation.Therapeutic innovation & regulatory science · 2025Article
- Prevalent Metformin Use in Adults With Diabetes and the Incidence of Long COVID: An EHR-Based Cohort Study From the RECOVER Program.Diabetes care · 2024Article
- Risk of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) Among Patients with Type 2 Diabetes Mellitus on Anti-Hyperglycemic Medications.Clinical epidemiology · 2024Article
- Old drug, new tricks: the utility of metformin in infection and vaccination responses to influenza and SARS-CoV-2 in older adults.Frontiers in aging · 2023Review
Corrections and comments
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Authors and funding
20 authors at 8 institutions in 2 countries.
Funding
Abstract
backgroundWhile 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.
methodsConducted 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.
results6,626 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.
conclusionsThere 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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