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0 0.5 1 1.5 2+ Mortality, MRS+AV+HD 29% Improvement Relative Risk Mortality, MRS only 20% Metformin for COVID-19  Silverii et al.  Prophylaxis Is prophylaxis with metformin beneficial for COVID-19? Retrospective 524 patients in Italy Lower mortality with metformin (not stat. sig., p=0.5) Silverii et al., J. Clinical Medicine, Mar 2024 Favors metformin Favors control

Is Metformin Use Associated with a More Favorable COVID-19 Course in People with Diabetes?

Silverii et al., Journal of Clinical Medicine, doi:10.3390/jcm13071874
Mar 2024  
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Metformin for COVID-19
3rd treatment shown to reduce risk in July 2020
*, now known with p < 0.00000000001 from 87 studies.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,000+ studies for 60+ treatments.
Retrospective 524 hospitalized COVID-19 patients with diabetes in Italy, showing lower risk of mortality with metformin use, without statistical significance. The results adjusted only for COVID-19 MRS differ between the text and Figure 2.
Although the 29% lower mortality is not statistically significant, it is consistent with the significant 34% lower mortality [29‑38%] from meta analysis of the 62 mortality results to date.
risk of death, 29.0% lower, OR 0.71, p = 0.50, treatment 220, control 304, adjusted for COVID-19 MRS, antivirals, heart disease, RR approximated with OR.
risk of death, 20.5% lower, OR 0.80, p = 0.34, treatment 220, control 304, adjusted for COVID-19 MRS only, RR approximated with OR.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Silverii et al., 24 Mar 2024, retrospective, Italy, peer-reviewed, 6 authors.
This PaperMetforminAll
Is Metformin Use Associated with a More Favorable COVID-19 Course in People with Diabetes?
Giovanni Antonio Silverii, Carlo Fumagalli, Renzo Rozzini, Marta Milani, Edoardo Mannucci, Niccolò Marchionni
Journal of Clinical Medicine, doi:10.3390/jcm13071874
Background: Diabetes Mellitus (DM) has been associated with a higher Coronavirus disease-19 (COVID-19) mortality, both in hospitalized patients and in the general population. A possible beneficial effect of metformin on the prognosis of COVID-19 has been reported in some observational studies, whereas other studies disagree. Methods: To investigate the possible effect of metformin on COVID-19 in-hospital mortality, we performed a retrospective study that included all SARS-CoV-2-positive patients with DM who were admitted to two Italian hospitals. In order to adjust for possible confounders accounting for the observed reduction of mortality in metformin users, we adopted the COVID-19 Mortality Risk Score (COVID-19 MRS) as a covariate. Results: Out of the 524 included patients, 33.4% died. A binomial logistic regression showed that metformin use was associated with a significant reduction in case fatality , p = 0.039), with no significant effect on the need for ventilation ], p = 0.146). After adjusting for COVID-19 MRS, metformin did not retain a significant association with in-hospital mortality , p = 0.342]. Conclusions: A beneficial effect of metformin on COVID-19 was not proven after adjusting for confounding factors. The use of validated tools to stratify the risk for COVID-19 severe disease and death, such as COVID-19 MRS, may be useful to better explore the potential association of medications and comorbidities with COVID-19 prognosis.
Author Contributions: G.A.S. was involved in the design, data collection, analysis, and writing of the manuscript; C.F., M.M., and R.R. were involved in patient s enrollment and data collection; E.M. and N.M. were involved in the design, analysis, writing of the manuscript, and manuscript revision. The corresponding author had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors have read and agreed to the published version of the manuscript. Funding: No Funding was provided for this research. This research was performed as a part of the institutional activity of the units, with no specific funding. All expenses, including salaries of the investigators, were covered by public research funds assigned to the units. Institutional Review Board Statement: The study was conducted according to the guidelines of the Declaration of Helsinki and its protocol approved by the local Ethical Review Board (Comitato Area Vasta Centro, CARE-COVID19 AOU Careggi Protocol 00/08761 15 April 2020). Informed Consent Statement: Each patient provided an informed oral consent which was recorded during the 1-month telephone interview. Conflicts of Interest: G.A. Silverii reports personal fees from Astra Zeneca, Eli Lilly, and Novo Nordisk outside the submitted work; E. Mannucci reports grants and personal fees from Astra Zeneca, Boehringer Ingelheim, Novo Nordisk, Eli Lilly, Genentech, Molteni, Merck,..
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