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0 0.5 1 1.5 2+ Mortality 47% Improvement Relative Risk Metformin for COVID-19  Sun et al.  META ANALYSIS Favors metformin Favors control

Is Metformin Use Associated With a Decreased Mortality for COVID-19 Diabetic Patients? A Meta-Analysis

Sun et al., Journal of the Endocrine Society, doi:10.1210/jendso/bvab048.709
May 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 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.
Meta analysis of 8 studies with 11,169 participants showing lower mortality with metformin use.
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, 47.0% lower, OR 0.53, p = 0.005, RR approximated with OR.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Sun et al., 1 May 2021, peer-reviewed, 5 authors.
This PaperMetforminAll
Is Metformin Use Associated With a Decreased Mortality for COVID-19 Diabetic Patients? A Meta-Analysis
MD, MSc Chenyu Sun, DO Ce Cheng, MD Keun Young Kim, Mubashir Ayaz, MD Reveena Manem
included. All included studies were considered moderate to high quality. No decreased mortality of COVID-19 diabetic patients was found among DPP-4 users (OR 0.86, 95%CI: 0.22,3.41, P=0.083, I 2 =81%). In the subgroup analysis, studies in Asia (OR 3.11, 95%CI: 0.78, 12.34, P=0.001, I 2 =70%) did not found reduced mortality, whereas studies in Europe (OR 0.36, 95%CI: 0.23, 0.56, P<0.00001, I 2 =0%) were associated with reduced mortality. Based on study designs, the four case-control studies (OR 1.27, 95%CI: 0.27, 5.93, P=0.76, I 2 =89%) did not find reduced mortality, but one cohort study (OR 0.13, 95%CI: 0.02, 0.84, P=0.03) showed a reduced mortality. The four studies investigating Type 2 Diabetes Mellitus (T2DM) did found reduced mortality (OR 0.74, 95%CI: 0.13, 4.24, P=0.73, I 2 =90%). For sample size >200, reduced risk of mortality (OR 0.28, 95%CI: 0.07, 1.15, P=0.08, I 2 =32%) was found, however, for sample ≤200, no statistically significant association (OR 1.44, 95%CI: 0.23, 8.89, P=0.70, I 2 =93%) was found. Sensitivity analysis by changing models and omitting each study at a time confirm the stability of the result. Begg's test (z=-0.24, P=1.000) and Egger's test (t=0.56, P=0.618) did not detect a significant risk of publication bias. Conclusion: The current meta-analysis did not find reduced mortality for COVID-19 diabetic patients who take DPP-4. However, subgroup-analyses found reduced mortality in Europe. More high-quality original studies are needed to further explore the association between DPP-4 use and the mortality risk of COVID-19.
{ 'DOI': '10.1210/jendso/bvab048.709', 'ISSN': ['2472-1972'], 'URL': '', 'abstract': '<jats:title>Abstract</jats:title>\n' ' <jats:p>Introduction: Coronavirus disease 2019 (COVID-19) has been spreading ' 'globally for more than half a year. Previous studies remain controversial regarding whether ' 'metformin is associated with reduced risk for COVID-19 diabetic patients. Thus, this ' 'meta-analysis is performed. Method: A comprehensive literature search on PubMed and Web of ' 'Science was conducted to identify all relevant studies published prior to October 2020 ' 'according to the established inclusion criteria. This meta-analysis was reported in ' 'conformity to the Preferred Reporting Project declared by the Systematic Review and ' 'Meta-Analysis (PRISMA). The quality assessment was performed by the Newcastle-Ottawa Scale ' '(NOS). The pooled odds ratio (OR) and 95% confidence intervals (CI) were calculated to ' 'estimate the association between metformin use and mortality for COVID-19 patients. A ' 'random-effect or fixed-effect model was used based on heterogeneity significance. Subgroup ' 'analysis was performed based on in-hospital-use or home-use, and different sample sizes. ' 'Sensitivity analysis and publication bias detection were also performed. All statistical ' 'analyses were performed using RevMan software (version 5.3; Cochrane library) and STATA 12.0 ' 'statistical software (Stata Corp., College Station, TX), and all P values were two-tailed, ' 'the test level was 0.05. Result: 97 articles were obtained from the database search, and 5 ' 'articles obtained from other sources. 8 articles involving 11,169 participants were included. ' 'Most studies were considered moderate quality. A statistically significant association ' 'between metformin use and decreased mortality of COVID-19 patients was found (OR 0.53, 95%CI: ' '0.34, 0.83, P=0.005, I2=77%). In the subgroup analyses, home-use of metformin was also ' 'associated with a reduced risk of mortality (OR 0.54, 95%CI: 0.35, 0.84, P=0.006, I2=66%), ' 'and one study reporting in-hospital use did not find reduced mortality among COVID-19 ' 'patients taking metformin (OR 1.65, 95%CI: 0.71, 3.86, P=0.247). For sample size ' '&amp;gt;1,000, no statistically significant reduced risk of mortality (OR 0.84, 95%CI: 0.57, ' '1.26, P=0.41, I2=73%) was found, however, for sample ≤1,000, a statistically significant ' 'reduced risk of mortality (OR 0.29, 95%CI: 0.19, 0.44 P&amp;lt;0.00001, I2=0%) was found. ' 'Sensitivity analysis by change fixed-effect models to random-effect models and by omitting ' 'each study at a time confirmed the relative stability of the result. Begg’s test (z=0.37, ' 'P=0.711) and Egger’s test (t=-1.98, P=0.096) did not detect a significant risk of publication ' 'bias. Conclusion: The current meta-analysis demonstrates that metformin use is associated ' 'with decreased mortality for COVID-19 diabetic patients. However, only one study ' 'investigating the in-hospital use of metformin. More high-quality original studies are needed ' 'to further explore the association between metformin use and mortality risk of ' 'COVID-19.</jats:p>', 'author': [ { 'affiliation': [{'name': 'AMITA Health Saint Joseph Hospital Chicago, Chicago, IL, USA'}], 'family': 'Sun', 'given': 'Chenyu', 'sequence': 'first'}, { 'affiliation': [ { 'name': 'University of Arizona College of Medicine at South Campus, ' 'Tucson, AZ, USA'}], 'family': 'Cheng', 'given': 'Ce', 'sequence': 'additional'}, { 'affiliation': [{'name': 'AMITA Health Saint Joseph Hospital Chicago, Chicago, IL, USA'}], 'family': 'Kim', 'given': 'Keun Young', 'sequence': 'additional'}, { 'affiliation': [{'name': 'AMITA Health Saint Joseph Hospital Chicago, Chicago, IL, USA'}], 'family': 'Ahmed', 'given': 'Mubashir Ayaz', 'sequence': 'additional'}, { 'affiliation': [{'name': 'AMITA Health Saint Joseph Hospital Chicago, Chicago, IL, USA'}], 'family': 'Manem', 'given': 'Reveena', 'sequence': 'additional'}], 'container-title': 'Journal of the Endocrine Society', 'content-domain': {'crossmark-restriction': False, 'domain': []}, 'created': {'date-parts': [[2021, 5, 3]], 'date-time': '2021-05-03T05:01:45Z', 'timestamp': 1620018105000}, 'deposited': { 'date-parts': [[2021, 7, 10]], 'date-time': '2021-07-10T06:49:10Z', 'timestamp': 1625899750000}, 'indexed': {'date-parts': [[2022, 3, 29]], 'date-time': '2022-03-29T03:01:15Z', 'timestamp': 1648522875113}, 'is-referenced-by-count': 0, 'issue': 'Supplement_1', 'issued': {'date-parts': [[2021, 5, 1]]}, 'journal-issue': {'issue': 'Supplement_1', 'published-print': {'date-parts': [[2021, 5, 3]]}}, 'language': 'en', 'license': [ { 'URL': '', 'content-version': 'vor', 'delay-in-days': 2, 'start': { 'date-parts': [[2021, 5, 3]], 'date-time': '2021-05-03T00:00:00Z', 'timestamp': 1620000000000}}], 'link': [ { 'URL': '', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'syndication'}, { 'URL': '', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'member': '80', 'original-title': [], 'page': 'A348-A348', 'prefix': '10.1210', 'published': {'date-parts': [[2021, 5, 1]]}, 'published-online': {'date-parts': [[2021, 5, 3]]}, 'published-other': {'date-parts': [[2021, 5, 1]]}, 'published-print': {'date-parts': [[2021, 5, 3]]}, 'publisher': 'The Endocrine Society', 'reference-count': 0, 'references-count': 0, 'relation': {}, 'resource': {'primary': {'URL': ''}}, 'score': 1, 'short-title': [], 'source': 'Crossref', 'subject': [], 'subtitle': [], 'title': 'Is Metformin Use Associated With a Decreased Mortality for COVID-19 Diabetic Patients? A ' 'Meta-Analysis', 'type': 'journal-article', 'volume': '5'}
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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