{"doi":"10.1371/journal.pone.0271574","title":"Diabetes medications and associations with Covid-19 outcomes in the N3C database: A national retrospective cohort study","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.","journal":"PLoS ONE","year":2022,"id":277240,"datarank":0.32958368660043297,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.0,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9617,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":719606,"name":"Steve Johnson","orcid":"0000-0002-2983-6384","position":1,"is_corresponding":false},{"id":948281,"name":"Víctor García","orcid":"0000-0003-4507-3839","position":2,"is_corresponding":false},{"id":283094,"name":"Michael D. Evans","orcid":"0000-0001-7449-3993","position":3,"is_corresponding":false},{"id":621075,"name":"Jeremy Harper","orcid":"0000-0003-1244-8948","position":4,"is_corresponding":false},{"id":391138,"name":"Kenneth J. Wilkins","orcid":"0000-0003-0531-7165","position":5,"is_corresponding":false},{"id":867226,"name":"Jared D. Huling","orcid":"0000-0003-0670-4845","position":6,"is_corresponding":false},{"id":369851,"name":"Hemalkumar B. Mehta","orcid":"0000-0001-9134-6370","position":7,"is_corresponding":false},{"id":948792,"name":"Caleb Alexander","orcid":null,"position":8,"is_corresponding":false},{"id":110111,"name":"Jena Shaw Tronieri","orcid":"0000-0003-3587-4130","position":9,"is_corresponding":false},{"id":948793,"name":"Stephenie Hong","orcid":null,"position":10,"is_corresponding":false},{"id":273575,"name":"Anna R. Kahkoska","orcid":"0000-0003-2701-101X","position":11,"is_corresponding":false},{"id":814804,"name":"Joy Alamgir","orcid":null,"position":12,"is_corresponding":false},{"id":49900,"name":"Farrukh M. Koraishy","orcid":"0000-0001-6974-5674","position":13,"is_corresponding":false},{"id":891990,"name":"Katrina M Hartman","orcid":"0000-0001-6723-0423","position":14,"is_corresponding":false},{"id":948282,"name":"Kaifeng Yang","orcid":"0000-0002-3353-3298","position":15,"is_corresponding":false},{"id":948283,"name":"Trine J. Abrahamsen","orcid":"0000-0002-4508-2623","position":16,"is_corresponding":false},{"id":426828,"name":"Til Stürmer‎","orcid":"0000-0002-9204-7177","position":17,"is_corresponding":false},{"id":34495,"name":"John B. Buse","orcid":"0000-0002-9723-3876","position":18,"is_corresponding":false},{"id":948794,"name":"N3C core authors","orcid":null,"position":19,"is_corresponding":false},{"id":49889,"name":"Carolyn T. Bramante","orcid":"0000-0001-5858-2080","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:28:34.768552Z","pmid":"36395143","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}