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0 0.5 1 1.5 2+ Mortality 72% Improvement Relative Risk Metformin for COVID-19  Wallace et al.  Prophylaxis Is prophylaxis with metformin beneficial for COVID-19? Retrospective 8,173 patients in the USA Lower mortality with metformin (p<0.000001) Wallace et al., BMJ Open, December 2021 Favors metformin Favors control

Association of the patterns of use of medications with mortality of COVID-19 infection: a hospital-based observational study

Wallace et al., BMJ Open, doi:10.1136/bmjopen-2021-050051
Dec 2021  
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Metformin for COVID-19
3rd treatment shown to reduce risk in July 2020
*, now known with p < 0.00000000001 from 88 studies.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,100+ studies for 60+ treatments.
Retrospective 9,532 hospitalized COVID+ veterans in the USA, showing lower mortality with metformin use. The study provides results for use before, after, and before+after. Before+after should more accurately represent prophylaxis up to COVID-19 infection (and continued use). Before included use up to 2 years before, and after included use up to 60 days later.
Study covers metformin and famotidine.
risk of death, 72.0% lower, HR 0.28, p < 0.001, treatment 103 of 1,203 (8.6%), control 1,536 of 6,970 (22.0%), NNT 7.4, adjusted per study, before+after, propensity score weighting, Cox proportional hazards.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Wallace et al., 31 Dec 2021, retrospective, database analysis, USA, peer-reviewed, 6 authors.
This PaperMetforminAll
Association of the patterns of use of medications with mortality of COVID-19 infection: a hospital-based observational study
Dr Arthur W Wallace, Piera M Cirillo, James C Ryan, Nickilou Y Krigbaum, Anusha Badathala, Barbara A Cohn
BMJ Open, doi:10.1136/bmjopen-2021-050051
Objectives SARS-CoV-2 enters cells using the ACE2 receptor. Medications that affect ACE2 expression or function such as angiotensin receptor blockers (ARBs) and ACE inhibitors (ACE-I) and metformin have the potential to counter the dysregulation of ACE2 by the virus and protect against viral injury. Here, we describe COVID-19 survival associated with ACE-I, ARB and metformin use. Design This is a hospital-based observational study of patients with COVID-19 infection using logistic regression with correction for pre-existing conditions and propensity score weighted Cox proportional hazards models to estimate associations between medication use and mortality. Setting Medical record data from the US Veterans Affairs (VA) were used to identify patients with a reverse transcription PCR diagnosis of COVID-19 infection, to classify patterns of ACE inhibitors (ACE-I), ARB, beta blockers, metformin, famotidine and remdesivir use, and, to capture mortality. Participants 9532 hospitalised patients with COVID-19 infection followed for 60 days were analysed. Outcome measure Death from any cause within 60 days of COVID-19 diagnosis was examined. Results Discontinuation of ACE-I was associated with increased risk of death (OR: 1.4; 95% CI 1.2-1.7). Initiating (OR: 0.3; 95% CI 0.2-0.5) or continuous (OR: 0.6; 95% CI 0.5-0.7) ACE-I was associated with reduced risk of death. ARB and metformin associations were similar in direction and magnitude and also statistically significant. Results were unchanged when accounting for pre-existing morbidity and propensity score adjustment. Conclusions Recent randomised clinical trials support the safety of continuing ACE-I and ARB treatment in patients with COVID-19 where indicated. Our study extends these findings to suggest a possible COVID-19 survival benefit for continuing or initiating ACE-I, ARB and metformin medications. Randomised trials are appropriate to confirm or refute the therapeutic potential for ACE-I, ARBs and metformin.
Competing interests All authors have completed the ICMJE uniform disclosure form at AW, PC, NYK and BAC declare support from grants from Mercatus Center, George Mason University, and from UC Office of the President, during the conduct of the study. All authors declare no other competing interests, no relationships with any organisations that might have a financial interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research. Patient consent for publication Not applicable. Ethics approval This study involves human participants and was approved by the University of California San Francisco's Institutional Review Board (IRB), the San Francisco VA Research and Development (R&D) committee and the Public Health Institute's IRB (US VA IRB project number: 10-03609). This study uses existing data available from the US Department of Veterans Affairs Corporate Data Warehouse and does not require informed consent but does require IRB approval. Provenance and peer review Not commissioned; externally peer reviewed. Data availability statement Data may be obtained from a third party and are not publicly available. Data requests for access to the de-identified (anonymised) data must be submitted to AWW (the..
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