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

Metformin for COVID-19

3rd treatment shown to reduce risk in July 2020, now with p < 0.0000000001 from 114 studies.

No treatment is 100% effective.
Protocols combine treatments.

Meta analysis of 8 studies with 11,169 participants showing lower mortality with metformin use.
24 meta-analyses show significant improvements with metformin for mortality1-23, hospitalization7,13,23, progression1, and severity8,9,13.
Currently there are 114 metformin for COVID-19 studies, showing 36% lower mortality [32‑40%], 30% lower ventilation [13‑43%], 19% lower ICU admission [8‑28%], 18% lower hospitalization [12‑23%], and 5% fewer cases [-3‑12%].
OutcomeImprovementEffect · pTreatmentControl
risk of death 47.0% lower · OR 0.53 · p = 0.005** 47.0% lowerOR 0.53p = 0.005** , RR approximated with OR

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates. ** p < 0.01

Sun et al., 1 May 2021, peer-reviewed, 5 authors.
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
doi:10.1210/jendso/bvab048
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 record: { "DOI": "10.1210/jendso/bvab048.709", "ISSN": [ "2472-1972" ], "URL": "http://dx.doi.org/10.1210/jendso/bvab048.709", "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": "http://creativecommons.org/licenses/by-nc-nd/4.0/", "content-version": "vor", "delay-in-days": 2, "start": { "date-parts": [ [ 2021, 5, 3 ] ], "date-time": "2021-05-03T00:00:00Z", "timestamp": 1620000000000 } } ], "link": [ { "URL": "http://academic.oup.com/jes/article-pdf/5/Supplement_1/A348/37204936/bvab048.709.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "syndication" }, { "URL": "http://academic.oup.com/jes/article-pdf/5/Supplement_1/A348/37204936/bvab048.709.pdf", "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": "https://academic.oup.com/jes/article/5/Supplement_1/A348/6241444" } }, "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" }