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0 0.5 1 1.5 2+ Mortality 34% Improvement Relative Risk Metformin for COVID-19  Li et al.  META ANALYSIS Favors metformin Favors control

Metformin in Patients With COVID-19: A Systematic Review and Meta-Analysis

Li et al., Frontiers in Medicine, doi:10.3389/fmed.2021.704666
Aug 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.
Meta analysis of 19 studies showing metformin use associated with lower COVID-19 mortality and hospitalization.
13 meta analyses show significant improvements with metformin for mortality Hariyanto, Kan, Kow, Li, Lukito, Ma, Oscanoa, Parveen, Petrelli, Poly, Schlesinger, Yang, hospitalization Li, progression Yang, and severity Petrelli, Schlesinger.
Currently there are 88 metformin for COVID-19 studies, showing 34% lower mortality [29‑38%], 31% lower ventilation [13‑45%], 16% lower ICU admission [6‑25%], 18% lower hospitalization [11‑24%], and 5% fewer cases [-4‑13%].
risk of death, 34.0% lower, OR 0.66, p < 0.001, RR approximated with OR.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Li et al., 19 Aug 2021, peer-reviewed, 6 authors. Contact:,
This PaperMetforminAll
Metformin in Patients With COVID-19: A Systematic Review and Meta-Analysis
Yin Li, Xue Yang, Peijing Yan, Tong Sun, Zhi Zeng, Sheyu Li
Frontiers in Medicine, doi:10.3389/fmed.2021.704666
Importance/Background: The coronavirus disease (COVID-19) pandemic is a critical public health issue. Evidence has shown that metformin favorably influences COVID-19 outcomes. This study aimed to assess the benefits and risks of metformin in COVID-19 patients. Methods: We searched the PubMed, Embase, Cochrane Library, and Chinese Biomedical Literature Database from inception to February 18, 2021. Observational studies assessing the association between metformin use and the outcomes of COVID-19 patients were included. The primary outcome was mortality, and the secondary outcomes included intubation, deterioration, and hospitalization. Random-effects weighted models were used to pool the specific effect sizes. Subgroup analyses were conducted by stratifying the meta-analysis by region, diabetic status, the adoption of multivariate model, age, risk of bias, and timing for adding metformin. Results: We identified 28 studies with 2,910,462 participants. Meta-analysis of 19 studies showed that metformin is associated with 34% lower COVID-19 mortality [odds ratio (OR), 0.66; 95% confidence interval (CI), 0.56-0.78; I 2 = 67.9%] and 27% lower hospitalization rate (pooled OR, 0.73; 95% CI, 0.53-1.00; I 2 = 16.8%). However, we did not identify any subgroup effects. The meta-analysis did not identify statistically significant association between metformin and intubation and deterioration of COVID-19 (OR, 0.94; 95% CI, 0.77-1.16; I 2 = 0.0% for intubation and OR, 2.04; 95% CI, 0.65-6.34; I 2 = 79.4% for deterioration of COVID-19), respectively. Conclusions: Metformin use among COVID-19 patients was associated with a reduced risk of mortality and hospitalization. Our findings suggest a relative benefit for metformin use in nursing home and hospitalized COVID-19 patients. However, randomized controlled trials are warranted to confirm the association between metformin use and COVID-19 outcomes.
AUTHOR CONTRIBUTIONS YL, ZZ, and SL: conception or design. YL, XY, PY, and TS: acquisition, analysis, or interpretation. YL, XY, PY, TS, ZZ, and SL: drafting the work or revision and final approval of the manuscript. All authors contributed to the article and approved the submitted version. SUPPLEMENTARY MATERIAL The Supplementary Material for this article can be found online at: 2021.704666/full#supplementary-material Conflict of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher's Note: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Bonnet, Scheen, Understanding, and overcoming metformin gastrointestinal intolerance, Diabetes Obes Metab, doi:10.1111/dom.12854
Bramante, Buse, Tamaritz, Palacio, Cohen et al., Outpatient metformin use is associated with reduced severity of COVID-19 disease in adults with overweight or obesity, J Med Virol, doi:10.1002/jmv.26873
Bramante, Ingraham, Murray, Marmor, Hovertsen et al., Metformin and risk of mortality in patients hospitalised with COVID-19: a retrospective cohort analysis, Lancet Healthy Longev, doi:10.1016/S2666-7568(20)30033-7
Bramante, Ingraham, Murray, Marmor, Hovertsen et al., Observational study of metformin and risk of mortality in patients hospitalized with COVID-19, doi:10.1101/2020.06.19.20135095
Bramante, Tignanelli, Dutta, Jones, Tamariz et al., Non-alcoholic fatty liver disease (NAFLD) and risk of hospitalization for COVID-19, doi:10.1101/2020.09.01.20185850
Buse, Wexler, Tsapas, Rossing, Mingrone et al., update to: management of hyperglycemia in type 2 diabetes, 2018. a consensus report by the American diabetes association (ADA) and the European association for the study of diabetes (EASD), Diabetes Care, doi:10.2337/dci19-0066
Cancer, Fitzmaurice, Abate, Abbasi, Abbastabar et al., Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disabilityadjusted life-years for 29 cancer groups, 1990 to 2017: a systematic analysis for the global burden of disease study, JAMA Oncol, doi:10.1001/jamaoncol.2019.2996
Cariou, Hadjadj, Wargny, Pichelin, Al-Salameh et al., Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study, Diabetologia, doi:10.1007/s00125-020-05180-x
Cheng, Liu, Zhang, Lei, Qin et al., Metformin is associated with higher incidence of acidosis, but not mortality, in individuals with COVID-19 and pre-existing type 2 diabetes, Cell Metab, doi:10.1016/j.cmet.2020.08.013
Choi, Ahn, Ryu, Kim, Jang et al., Clinical characteristics and disease progression in early-stage COVID-19 patients in South Korea, J Clin Med, doi:10.3390/jcm9061959
Clark, Jit, Warren-Gash, Guthrie, Wang et al., Global, regional, and national estimates of the population at increased risk of severe COVID-19 due to underlying health conditions in 2020: a modelling study, Lancet Global Health, doi:10.1016/S2214-109X(20)30264-3
Crouse, Grimes, Li, Might, Ovalle et al., Metformin use is associated with reduced mortality in a diverse population with COVID-19 and diabetes, Front Endocrinol, doi:10.3389/fendo.2020.600439
Do, Kim, Park, Cho, Kang, Is there an association between metformin use and clinical outcomes in diabetes patients with COVID-19?, Diabetes Metab, doi:10.1016/j.diabet.2020.10.006
Gao, Liu, Zhong, Liu, Zhou et al., Risk of metformin in patients with type 2 diabetes with COVID-19: a preliminary retrospective report, Clin Transl Sci, doi:10.1111/cts.12897
Garber, Handelsman, Grunberger, Einhorn, Abrahamson et al., Consensus statement by the American association of clinical endocrinologists and American college of endocrinology on the comprehensive ttype 2 diabetes management algorithm -2020 executive summary, Endocr Pract, doi:10.4158/cs-2019-0472
Griffin, Leaver, Irving, Impact of metformin on cardiovascular disease: a meta-analysis of randomised trials among people with type 2 diabetes, Diabetologia, doi:10.1007/s00125-017-4337-9
Guan, Ni, Hu, Liang, Ou et al., Clinical characteristics of coronavirus disease 2019 in China, N Engl J Med, doi:10.1056/NEJMoa2002032
Hayek, Robert, Matar, Algarni, Alkubedan et al., Risk factors for hospital admission among COVID-19 patients with diabetes a study from Saudi Arabia, Saudi Med J, doi:10.15537/smj.2020.10.25419
Hoffmann, Kleine-Weber, Schroeder, Krüger, Herrler et al., SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor, Cell, doi:10.1016/j.cell.2020.02.052
Huang, Lim, Pranata, Diabetes mellitus is associated with increased mortality and severity of disease in COVID-19 pneumonia -a systematic review, meta-analysis, and meta-regression, Diabetes Metab Syndr, doi:10.1016/j.dsx.2020.04.018
Izzi-Engbeaya, Distaso, Amin, Yang, Idowu et al., Adverse outcomes in COVID-19 and diabetes: a retrospective cohort study from three London teaching hospitals, BMJ Open Diabetes Res Care, doi:10.1136/bmjdrc-2020-001858
Jiang, Chen, Yin, Liu, Yang et al., Association of metformin with mortality or ARDS in patients with COVID-19 and type 2 diabetes: a retrospective cohort study, Diabetes Res Clin Pract, doi:10.1016/j.diabres.2020.108619
Khunti, Knighton, Zaccardi, Bakhai, Barron et al., Prescription of glucose-lowering therapies and risk of COVID-19 mortality in people with type 2 diabetes: a nationwide observational study in England, Lancet Diabetes Endocrinol, doi:10.1016/S2213-8587(21)00050-4
Kichloo, Albosta, Dettloff, Wani, El-Amir et al., Telemedicine, the current COVID-19 pandemic and the future: a narrative review and perspectives moving forward in the USA, Fam Med Community Health, doi:10.1136/fmch-2020-000530
Kim, Jeon, Moon, Cho, Han et al., The clinical characteristics and outcomes of patients with moderate-to-severe coronavirus disease 2019 infection and diabetes in daegu, South Korea, Diabetes Metab J, doi:10.4093/dmj.2020.0146
Kow, Hasan, Mortality risk with preadmission metformin use in patients with COVID-19 and diabetes: a meta-analysis, J Med Virol, doi:10.1002/jmv.26498
Lalau, Al-Salameh, Hadjadj, Goronflot, Wiernsperger et al., Metformin use is associated with a reduced risk of mortality in patients with diabetes hospitalised for COVID-19, Diabetes Metab, doi:10.1016/j.diabet.2020.101216
Lalau, Kajbaf, Protti, Christensen, Broe, Metforminassociated lactic acidosis (MALA): moving towards a new paradigm, Diabetes Obes Metab, doi:10.1111/dom.12974
Lally, Tsoukas, Halladay, Neill, Gravenstein et al., Metformin is associated with decreased 30-day mortality among nursing home residents infected with SARS-CoV2, J Am Med Dir Assoc, doi:10.1016/j.jamda.2020.10.031
Li, Nemeth, Donnelly, Hapca, Zhou et al., Visit-to-visit HbA1c variability is associated with cardiovascular disease and microvascular complications in patients with newly diagnosed type 2 diabetes, Diabetes Care, doi:10.2337/dc19-0823
Li, Wei, Li, Mccowen, Xiong et al., Metformin use in diabetes prior to hospitalization: effects on mortality in COVID-19, Endocr Pract, doi:10.4158/EP-2020-0466
Li, Zong, Sun, Li, New evidence-based clinical practice guideline timely supports hospital infection control of coronavirus disease 2019, Precis Clin Med, doi:10.1093/pcmedi/pbaa008
Liu, Bai, Han, Jiang, Qiu et al., The association of diabetes and the prognosis of COVID-19 patients: a retrospective study, Diabetes Res Clin Pract, doi:10.1016/j.diabres.2020.108386
Liu, Li, Quan, Li, Vitamin B12 status in metformin treated patients: systematic review, PLoS ONE, doi:10.1371/journal.pone.0100379
Lukito, Pranata, Henrina, Lim, Lawrensia et al., The effect of metformin consumption on mortality in hospitalized COVID-19 patients: a systematic review and meta-analysis, Diabetes Metab Syndr, doi:10.1016/j.dsx.2020.11.006
Luo, Qiu, Liu, Liu, Zheng et al., Metformin treatment was associated with decreased mortality in COVID-19 patients with diabetes in a retrospective analysis, Am J Trop Med Hyg, doi:10.4269/ajtmh.20-0375
Matsiukevich, Piraino, Lahni, Hake, Wolfe et al., Metformin ameliorates gender-and age-dependent hemodynamic instability and myocardial injury in murine hemorrhagic shock, Biochim Biophys Acta Mol Basis Dis, doi:10.1016/j.bbadis.2017.05.027
Mccreight, Bailey, Pearson, Metformin, and the gastrointestinal tract, Diabetologia, doi:10.1007/s00125-015-3844-9
Mirsoleymani, Nekooghadam, Marzaleh, Peyravi, Soltani et al., Assessment of risk factors for severe coronavirus disease 2019 among Iranian patients, Iran Red Crescent Med J, doi:10.32592/ircmj.2020.22.9.72
Moher, Liberati, Tetzlaff, Altman, Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement, PLoS Med, doi:10.1371/journal.pmed.1000097
Nafakhi, Alareedh, Al-Buthabhak, Shaghee, Nafakhi et al., Predictors of adverse in-hospital outcome and recovery in patients with diabetes mellitus and COVID-19 pneumonia in Iraq, Diabetes Metab Syndr, doi:10.1016/j.dsx.2020.12.014
Orioli, Servais, Belkhir, Laterre, Thissen et al., Clinical characteristics and short-term prognosis of in-patients with diabetes and COVID-19: a retrospective study from an academic center in Belgium, Diabetes Metab Syndr, doi:10.1016/j.dsx.2020.12.020
Palmer, Tendal, Mustafa, Vandvik, Li et al., Sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials, BMJ, doi:10.1136/bmj.m4573
Park, Lee, Park, Park, Cheon et al., Sex-dependent difference in the effect of metformin on colorectal cancer-specific mortality of diabetic colorectal cancer patients, World J Gastroenterol, doi:10.3748/wjg.v23.i28.5196
Perez-Belmonte, Torres-Pena, Lopez-Carmona, Ayala-Gutierrez, Fuentes-Jimenez et al., Mortality and other adverse outcomes in patients with type 2 diabetes mellitus admitted for COVID-19 in association with glucose-lowering drugs: a nationwide cohort study, BMC Med, doi:10.1186/s12916-020-01832-2
Petrie, Rossing, Campbell, Metformin, and cardiorenal outcomes in diabetes: a reappraisal, Diabetes Obes Metab, doi:10.1111/dom.13984
Simonnet, Chetboun, Poissy, Raverdy, Noulette et al., High prevalence of obesity in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) requiring invasive mechanical ventilation, Obesity, doi:10.1002/oby.22831
Stang, Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses, Eur J Epidemiol, doi:10.1007/s10654-010-9491-z
Tan, Wang, Liu, Shi, Zhou et al., Long-acting metformin vs. Metformin immediate release in patients with type 2 diabetes: a systematic review, Front Pharmacol, doi:10.3389/fphar.2021.669814
Ursini, Ciaffi, Landini, Meliconi, COVID-19, and diabetes: Is metformin a friend or foe?, Diabetes Res Clin Pract, doi:10.1016/j.diabres.2020.108167
Vj, Illescas-Montes, Puerta-Puerta, Ruiz, Melguizo-Rodríguez, SARS-CoV-2 infection: the role of cytokines in COVID-19 disease, Cytokine Growth Factor Rev, doi:10.1016/j.cytogfr.2020.06.001
Wang, Cooper, Gokhale, Acosta-Mena, Dhalla et al., Association of metformin with susceptibility to COVID-19 in people with type 2 diabetes, J Clin Endocrinol Metab, doi:10.1210/clinem/dgab067
Wang, Gao, Zhang, Huang, Zhang et al., Prevalence ethnic pattern of diabetes prediabetes in China in 2013, JAMA, doi:10.1001/jama.2017.7596
Wang, Van Oekelen, Mouhieddine, Valle, Richter et al., A tertiary center experience of multiple myeloma patients with COVID-19: lessons learned and the path forward, J Hematol Oncol, doi:10.1186/s13045-020-00934-x
Yang, Tao, Peng, Zhao, Li et al., High-sensitivity C-reactive protein and risk of type 2 diabetes: a nationwide cohort study and updated meta-analysis, Diabetes Metab Res Rev, doi:10.1002/dmrr.3446
Yitao, Mu, Ling, Shiyao, Jiaojie et al., Predictors of clinical deterioration in non-severe patients with COVID-19: a retrospective cohort study, Curr Med Res Opin, doi:10.1080/03007995.2021.1876005
Zhang, Dong, Martin, He, Gongol et al., AMPactivated protein kinase phosphorylation of angiotensin-converting enzyme 2 in endothelium mitigates pulmonary hypertension, Am J Respir Crit Care Med, doi:10.1164/rccm.201712-2570OC
Zhang, Li, Li, Li, Ren et al., Metformin treatment and homocysteine: a systematic review and meta-analysis of randomized controlled trials, Nutrients, doi:10.3390/nu8120798
Zhang, Wang, Zhu, Mao, Bai et al., Risk factors for poor outcomes of diabetes patients with COVID-19: a single-center, retrospective study in early outbreak in China, Front Endocrinol, doi:10.3389/fendo.2020.571037
Zhou, Zhang, Zhang, Zhou, Li et al., Population diversity of cardiovascular outcome trials and real-world patients with diabetes in a Chinese tertiary hospital, Chin Med J, doi:10.1097/CM9.0000000000001407
Zhu, Zhong, Li, Li, Pang, Clinicopathological characteristics of 8697 patients with COVID-19 in China: a meta-analysis, Fam Med Community Health, doi:10.1136/fmch-2020-000406
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