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0 0.5 1 1.5 2+ Mortality 22% Improvement Relative Risk Metformin for COVID-19  Ganesh et al.  META ANALYSIS c19early.org Favors metformin Favors control

Does metformin affect outcomes in COVID‐19 patients with new or pre‐existing diabetes mellitus? A systematic review and meta‐analysis

Ganesh et al., British Journal of Clinical Pharmacology, doi:10.1111/bcp.15258, PROSPERO CRD42020221842
Feb 2022  
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Metformin for COVID-19
3rd treatment shown to reduce risk in July 2020
 
*, now known with p < 0.00000000001 from 89 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. c19early.org
Meta analysis of 32 cohort studies with 2,916,231 patients showing significantly lower mortality with metformin treatment in COVID-19 patients with diabetes, with an unadjusted odds ratio of 0.61 (95% CI: 0.53-0.71) and an adjusted odds ratio of 0.78 (95% CI: 0.69-0.88). The study suggests metformin may improve outcomes in these patients through multiple mechanisms, including attenuating cytokine storms, improving adaptive and innate immunity, and decreasing viral entry.
22 meta analyses show significant improvements with metformin for mortality Chen, Ganesh, Han, Hariyanto, Kan, Kow, Li, Lukito, Ma, Nassar, Nguyen, Oscanoa, Parveen, Petrelli, Poly, Scheen, Schlesinger, Song, Sun, Yang, Zhan, hospitalization Li, Song, progression Yang, and severity Petrelli, Schlesinger, Song.
Currently there are 89 metformin for COVID-19 studies, showing 34% lower mortality [29‑39%], 33% lower ventilation [17‑46%], 16% lower ICU admission [6‑25%], 18% lower hospitalization [11‑24%], and 5% fewer cases [-4‑13%].
risk of death, 22.0% lower, OR 0.78, p < 0.001, RR approximated with OR.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Ganesh et al., 23 Feb 2022, peer-reviewed, 2 authors, trial PROSPERO CRD42020221842. Contact: adithanganesh321@gmail.com.
This PaperMetforminAll
Does metformin affect outcomes in COVID‐19 patients with new or pre‐existing diabetes mellitus? A systematic review and meta‐analysis
Adithan Ganesh, Michael D Randall
British Journal of Clinical Pharmacology, doi:10.1111/bcp.15258
Aims: The COVID-19 pandemic is a global public health emergency and patients with diabetes mellitus (DM) are disproportionately affected, exhibiting more severe outcomes. Recent studies have shown that metformin is associated with improved outcomes in patients with COVID-19 and DM and may be a potential candidate for drug repurposing. We aimed to investigate the effects of metformin on outcomes in patients with COVID-19 and DM. Methods: Databases (PubMed, Scopus, Web of Science, EMBASE, Clinicaltrials.gov and Cochrane library) were searched up to 10 April 2021 for studies reporting data on metformin use in COVID-19 patients with DM. The risk of bias was assessed using the Newcastle-Ottawa scale. Certainty of evidence was rated using the GRADE approach. The primary outcome was mortality reported as odds ratio (OR). A random-effects meta-analysis was carried out on both unadjusted and adjusted ORs. This study is registered with PROSPERO, CRD42020221842. Results: In total, 2 916 231 patients from 32 cohort studies were included in the quantitative and qualitative synthesis. The meta-analysis showed that metformin was significantly associated with lower mortality in COVID-19 patients with DM in both unadjusted (OR 0.61 [95% confidence interval: 0.53-0.71], P < .00001, I 2 = 70%) and adjusted (OR 0.78 [95% confidence interval: 0.69-0.88], P < .00001, I 2 = 67%) models. Conclusion: Poor outcomes in COVID-19 patients with DM can be attributed to inadequate glycaemic control and weakened immune responses. Metformin has multiple effects that can improve outcomes in patients with DM and our findings highlight a possible role of its use. However, robust randomised trials are needed to thoroughly assess its use.
COMPETING INTERESTS None.
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{ 'DOI': '10.1111/bcp.15258', 'ISSN': ['0306-5251', '1365-2125'], 'URL': 'http://dx.doi.org/10.1111/bcp.15258', 'abstract': '<jats:sec><jats:title>Aims</jats:title><jats:p>The COVID‐19 pandemic is a global public ' 'health emergency and patients with diabetes mellitus (DM) are disproportionately affected, ' 'exhibiting more severe outcomes. Recent studies have shown that metformin is associated with ' 'improved outcomes in patients with COVID‐19 and DM and may be a potential candidate for drug ' 'repurposing. We aimed to investigate the effects of metformin on outcomes in patients with ' 'COVID‐19 and ' 'DM.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Databases (PubMed, ' 'Scopus, Web of Science, EMBASE, <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ' 'xlink:href="http://Clinicaltrials.gov">Clinicaltrials.gov</jats:ext-link> and Cochrane ' 'library) were searched up to 10 April 2021 for studies reporting data on metformin use in ' 'COVID‐19 patients with DM. The risk of bias was assessed using the Newcastle–Ottawa scale. ' 'Certainty of evidence was rated using the GRADE approach. The primary outcome was mortality ' 'reported as odds ratio (OR). A random‐effects meta‐analysis was carried out on both ' 'unadjusted and adjusted ORs. This study is registered with PROSPERO, ' 'CRD42020221842.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>In ' 'total, 2\u2009916\u2009231 patients from 32 cohort studies were included in the quantitative ' 'and qualitative synthesis. The meta‐analysis showed that metformin was significantly ' 'associated with lower mortality in COVID‐19 patients with DM in both unadjusted (OR 0.61 [95% ' 'confidence interval: 0.53–0.71], <jats:italic>P</jats:italic>\xa0&lt;\u2009.00001, ' '<jats:italic>I</jats:italic><jats:sup>2</jats:sup>\xa0=\u200970%) and adjusted (OR 0.78 [95% ' 'confidence interval: 0.69–0.88], <jats:italic>P</jats:italic>\xa0&lt;\u2009.00001, ' '<jats:italic>I</jats:italic><jats:sup>2</jats:sup>\xa0=\u200967%) ' 'models.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Poor outcomes ' 'in COVID‐19 patients with DM can be attributed to inadequate glycaemic control and weakened ' 'immune responses. Metformin has multiple effects that can improve outcomes in patients with ' 'DM and our findings highlight a possible role of its use. 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' 'A systematic review and meta‐analysis', 'type': 'journal-article', 'volume': '88'}
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