{"doi":"10.17615/bbtc-nx39","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":"UNC Libraries","year":2022,"id":313434,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9606,"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":1012165,"name":"A. Kahkoska","orcid":null,"position":1,"is_corresponding":false},{"id":65985,"name":"Michael Evans","orcid":null,"position":2,"is_corresponding":false},{"id":1012166,"name":"N C core authors","orcid":null,"position":3,"is_corresponding":false},{"id":1012167,"name":"J. Alamgir","orcid":null,"position":4,"is_corresponding":false},{"id":1012168,"name":"S.G. Johnson","orcid":null,"position":5,"is_corresponding":false},{"id":1012169,"name":"Jack Harper","orcid":null,"position":6,"is_corresponding":false},{"id":1012170,"name":"Kyoung-Ock Yang","orcid":null,"position":7,"is_corresponding":false},{"id":1012171,"name":"VICTOR BARRETO GARCIA","orcid":null,"position":8,"is_corresponding":false},{"id":1012172,"name":"C.T. Bramante","orcid":null,"position":9,"is_corresponding":false},{"id":338164,"name":"J.B. Buse","orcid":null,"position":10,"is_corresponding":false},{"id":541598,"name":"T. Stürmer","orcid":null,"position":11,"is_corresponding":false},{"id":1012173,"name":"K.J. Wilkins","orcid":null,"position":12,"is_corresponding":false},{"id":1012174,"name":"C. Alexander","orcid":null,"position":13,"is_corresponding":false},{"id":1012175,"name":"T. Abrahamsen","orcid":null,"position":14,"is_corresponding":false},{"id":1012176,"name":"J.D. Huling","orcid":null,"position":15,"is_corresponding":false},{"id":1012177,"name":"K. Hartman","orcid":null,"position":16,"is_corresponding":false},{"id":1012178,"name":"J.S. Tronieri","orcid":null,"position":17,"is_corresponding":false},{"id":1012179,"name":"F. Koraishy","orcid":null,"position":18,"is_corresponding":false},{"id":545035,"name":"H. Mehta","orcid":null,"position":19,"is_corresponding":false},{"id":1012164,"name":"S. Hong","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T00:33:44.454239Z","pmid":null,"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":[]}