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Outcome and death risk of diabetes patients with Covid-19 receiving pre-hospital and in-hospital metformin therapies

Tamura et al., Diabetology & Metabolic Syndrome, doi:10.1186/s13098-021-00695-8
Jul 2021  
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0 0.5 1 1.5 2+ Mortality 97% Improvement Relative Risk Metformin for COVID-19  Tamura et al.  LATE TREATMENT Is late treatment with metformin beneficial for COVID-19? Retrospective 188 patients in Brazil (March - November 2020) Lower mortality with metformin (p=0.019) c19early.org Tamura et al., Diabetology & Metabolic.., Jul 2021 Favors metformin Favors control
Metformin for COVID-19
3rd treatment shown to reduce risk in July 2020
 
*, now known with p < 0.00000000001 from 91 studies.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,200+ studies for 70+ treatments. c19early.org
Retrospective 188 hospitalized patients in Brazil, showing lower risk of mortality with metformin use. Authors note that, although pre-hospital metformin use improved clinical parameters at admission, continuous use during hospitalization is essential. Patients that used pre-hospital metformin therapy but interrupted the treatment during hospitalization showed higher mortality than those that continued metformin therapy.
Study covers HCQ and metformin.
risk of death, 96.6% lower, OR 0.03, p = 0.02, treatment 115, control 73, adjusted per study, in-hospital use, multivariable, RR approximated with OR.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Tamura et al., 13 Jul 2021, retrospective, Brazil, peer-reviewed, 4 authors, study period 10 March, 2020 - 13 November, 2020.
This PaperMetforminAll
Outcome and death risk of diabetes patients with Covid-19 receiving pre-hospital and in-hospital metformin therapies
Rodrigo Esaki Tamura, Said Muhammad Said, Leticia Mussin De Freitas, Ileana Gabriela Sanchez Rubio
Diabetology & Metabolic Syndrome, doi:10.1186/s13098-021-00695-8
Background: COVID-19 has stroke Brazil harshly, deaths by COVID-19 in Brazil represent almost 13% of the total deaths by COVID-19 in the world, even though Brazilian population represents only 2.6% of the world population. Our aim in this study was to evaluate death and intubation outcomes and risk factors associated with COVID-19, and treatment options focusing on diabetes patients and the use of metformin pre-admission and during hospitalization. Methods: In this Brazilian single-center study we evaluated 1170 patients hospitalized due to COVID-19. Diabetes patients (n = 188) were divided based on their use of pre-hospital and in-hospital metformin (non-met-group and met-group). Results: In the total cohort most comorbidities were risk factors for orotracheal intubation and death. The use of chloroquine/hydroxychloroquine was significantly associated with increased death and intubation risk in uni-and multivariate analysis. Diabetes patients showed worst clinical feature compared with non-diabetes patients. In-hospital non-met-group had increased mortality (20.5%) compared to met-group (3.5%) (p = 0.0002) and univariable cox proportion hazard regression indicated in-hospital metformin reduced mortality (HR = 0.325, p = 0.035). Patients that used pre-hospital metformin showed lower severity parameters at hospital admission. (met-group: 2.45 ± 2.5; nonmet-group: 4.25 ± 3.4). In all the groups older patients showed more severe clinical conditions and high risk of death and intubation. Conclusion: Even though this is a single-center study, results from other reports have shown a similar trend, indicating that patients that used metformin during hospitalization have a better prognosis and reduced risk of death.
Supplementary Information The online version contains supplementary material available at https:// doi. org/ 10. 1186/ s13098-021-00695-8. Additional file 1: Table S1 . Comparison of demographic and clinical characteristics of diabetes and non-diabetic patients. Table S2 . Clinical characteristics of diabetes' patients compared by age. Table S3 . Clinical characteristics of diabetes patients compared between dead and nondead patients. Table S4 . Univariate in-hospital risk factor associated with in-hospital mortality and orotracheal intubation of diabetes patients. Authors' contributions RET designed and wrote the manuscript; SMS collected the data; LMF organized the data; IGSR designed, made the statistical analysis and revised the manuscript. All authors read and approved the final manuscript. Declarations Ethics approval and consent to participate This study was approved by the Ethical Committee of the Santa Catarina Hospital and UNIFESP (CAAE 43014721.7.0000. 5505). Consent for publication All authors consent the publication. Competing interests There are no competing interests. • thorough peer review by experienced researchers in your field • rapid publication on acceptance • support for research data, including large and complex data types • gold Open Access which fosters wider collaboration and increased citations maximum visibility for your research: over 100M website views per year Publisher's Note Springer Nature remains neutral with regard to..
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' 'Predictors of hospital discharge and mortality in patients with diabetes ' 'and COVID-19: updated results from the nationwide CORONADO study. ' 'Diabetologia. 2021;64(4):778–94.', 'journal-title': 'Diabetologia'}, { 'issue': '1', 'key': '695_CR18', 'doi-asserted-by': 'publisher', 'first-page': 'e001343', 'DOI': '10.1136/bmjdrc-2020-001343', 'volume': '8', 'author': 'Y Yan', 'year': '2020', 'unstructured': 'Yan Y, Yang Y, Wang F, Ren H, Zhang S, Shi X, et al. Clinical ' 'characteristics and outcomes of patients with severe covid-19 with ' 'diabetes. BMJ Open Diabetes Res Care. 2020;8(1):e001343.', 'journal-title': 'BMJ Open Diabetes Res Care.'}, { 'issue': '1', 'key': '695_CR19', 'doi-asserted-by': 'publisher', 'first-page': '69', 'DOI': '10.4269/ajtmh.20-0375', 'volume': '103', 'author': 'P Luo', 'year': '2020', 'unstructured': 'Luo P, Qiu L, Liu Y, Liu XL, Zheng JL, Xue HY, et al. Metformin ' 'treatment was associated with decreased mortality in COVID-19 patients ' 'with diabetes in a retrospective analysis. Am J Trop Med Hyg. ' '2020;103(1):69–72.', 'journal-title': 'Am J Trop Med Hyg'}, { 'issue': '1', 'key': '695_CR20', 'doi-asserted-by': 'publisher', 'first-page': '33', 'DOI': '10.1016/j.dsx.2020.12.014', 'volume': '15', 'author': 'H Nafakhi', 'year': '2020', 'unstructured': 'Nafakhi H, Alareedh M, Al-Buthabhak K, Shaghee F, Nafakhi A, Kasim S. ' 'Predictors of adverse in-hospital outcome and recovery in patients with ' 'diabetes mellitus and COVID-19 pneumonia in Iraq. Diabetes Metab Syndr. ' '2020;15(1):33–8.', 'journal-title': 'Diabetes Metab Syndr'}, { 'issue': '1', 'key': '695_CR21', 'doi-asserted-by': 'publisher', 'first-page': '193', 'DOI': '10.1016/j.jamda.2020.10.031', 'volume': '22', 'author': 'MA Lally', 'year': '2021', 'unstructured': 'Lally MA, Tsoukas P, Halladay CW, O’Neill E, Gravenstein S, Rudolph JL. ' 'Metformin is associated with decreased 30-day mortality among nursing ' 'home residents infected with SARS-CoV2. J Am Med Dir Assoc. ' '2021;22(1):193–8.', 'journal-title': 'J Am Med Dir Assoc'}, { 'issue': '1', 'key': '695_CR22', 'doi-asserted-by': 'publisher', 'first-page': '35', 'DOI': '10.14341/probl12458', 'volume': '66', 'author': 'MV Shestakova', 'year': '2020', 'unstructured': 'Shestakova MV, Vikulova OK, IsakovMcapital AC, Dedov II. Diabetes and ' 'COVID-19: analysis of the clinical outcomes according to the data of the ' 'Russian diabetes registry. Probl Endokrinol (Mosk). 2020;66(1):35–46.', 'journal-title': 'Probl Endokrinol (Mosk)'}, { 'key': '695_CR23', 'doi-asserted-by': 'publisher', 'author': 'JY Do', 'year': '2020', 'unstructured': 'Do JY, Kim SW, Park JW, Cho KH, Kang SH. Is there an association between ' 'metformin use and clinical outcomes in diabetes patients with COVID-19? ' 'Diabetes Metab. 2020. https://doi.org/10.1016/j.diabet.2020.10.006.', 'journal-title': 'Diabetes Metab.', 'DOI': '10.1016/j.diabet.2020.10.006'}, { 'issue': '1', 'key': '695_CR24', 'doi-asserted-by': 'publisher', 'first-page': '359', 'DOI': '10.1186/s12916-020-01832-2', 'volume': '18', 'author': 'LM Perez-Belmonte', 'year': '2020', 'unstructured': 'Perez-Belmonte LM, Torres-Pena JD, Lopez-Carmona MD, Ayala-Gutierrez MM, ' 'Fuentes-Jimenez F, Huerta LJ, 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. 2020;18(1):359.', 'journal-title': 'BMC Med'}, { 'issue': '6', 'key': '695_CR25', 'doi-asserted-by': 'publisher', 'first-page': '1089', 'DOI': '10.1007/s41999-020-00373-4', 'volume': '11', 'author': 'P Knopp', 'year': '2020', 'unstructured': 'Knopp P, Miles A, Webb TE, McLoughlin BC, Mannan I, Raja N, et al. ' 'Presenting features of COVID-19 in older people: relationships with ' 'frailty, inflammation and mortality. Eur Geriatr Med. ' '2020;11(6):1089–94.', 'journal-title': 'Eur Geriatr Med'}, { 'issue': '11', 'key': '695_CR26', 'doi-asserted-by': 'publisher', 'first-page': 'e0241824', 'DOI': '10.1371/journal.pone.0241824', 'volume': '15', 'author': 'FK Ho', 'year': '2020', 'unstructured': 'Ho FK, Petermann-Rocha F, Gray SR, Jani BD, Katikireddi SV, Niedzwiedz ' 'CL, et al. Is older age associated with COVID-19 mortality in the ' 'absence of other risk factors? General population cohort study of ' '470,034 participants. PLoS One. 2020;15(11):e0241824.', 'journal-title': 'PLoS One.'}, { 'key': '695_CR27', 'doi-asserted-by': 'publisher', 'author': 'DN Vita', 'year': '2021', 'unstructured': 'Vita DN, Scotti L, Cammarota G, Racca F, Pissaia C, Maestrone C, et al. ' 'Predictors of intubation in COVID-19 patients treated with out-of-ICU ' 'continuous positive airway pressure. Pulmonology. 2021. ' 'https://doi.org/10.1016/j.pulmoe.2020.12.010.', 'journal-title': 'Pulmonology', 'DOI': '10.1016/j.pulmoe.2020.12.010'}, { 'issue': '9', 'key': '695_CR28', 'doi-asserted-by': 'publisher', 'first-page': '782', 'DOI': '10.1016/S2213-8587(20)30238-2', 'volume': '8', 'author': 'M Apicella', 'year': '2020', 'unstructured': 'Apicella M, Campopiano MC, Mantuano M, Mazoni L, Coppelli A, Del Prato ' 'S. COVID-19 in people with diabetes: understanding the reasons for worse ' 'outcomes. Lancet Diabetes Endocrinol. 2020;8(9):782–92.', 'journal-title': 'Lancet Diabetes Endocrinol'}, { 'key': '695_CR29', 'first-page': 'CD013587', 'volume': '2', 'author': 'B Singh', 'year': '2021', 'unstructured': 'Singh B, Ryan H, Kredo T, Chaplin M, Fletcher T. Chloroquine or ' 'hydroxychloroquine for prevention and treatment of COVID-19. Cochrane ' 'Database Syst Rev. 2021;2:CD013587.', 'journal-title': 'Cochrane Database Syst Rev.'}, { 'key': '695_CR30', 'doi-asserted-by': 'publisher', 'first-page': '356', 'DOI': '10.1093/toxsci/kfaa194', 'volume': '180', 'author': 'P Jordaan', 'year': '2021', 'unstructured': 'Jordaan P, Dumotier B, Traebert M, Miller PE, Ghetti A, Urban L, et al. ' 'Cardiotoxic potential of hydroxychloroquine, chloroquine and ' 'azithromycin in adult human primary cardiomyocytes. Toxicol Sci. ' '2021;180:356–68.', 'journal-title': 'Toxicol Sci'}, { 'issue': '1', 'key': '695_CR31', 'doi-asserted-by': 'publisher', 'first-page': '16', 'DOI': '10.1016/j.jacep.2020.07.016', 'volume': '7', 'author': "TF O'Connell", 'year': '2021', 'unstructured': 'O’Connell TF, Bradley CJ, Abbas AE, Williamson BD, Rusia A, Tawney AM, ' 'et al. Hydroxychloroquine/azithromycin therapy and QT prolongation in ' 'hospitalized patients with COVID-19. JACC Clin Electrophysiol. ' '2021;7(1):16–25.', 'journal-title': 'JACC Clin Electrophysiol'}, { 'issue': '3', 'key': '695_CR32', 'doi-asserted-by': 'publisher', 'first-page': '354', 'DOI': '10.1016/j.mehy.2003.12.004', 'volume': '62', 'author': 'GE Parris', 'year': '2004', 'unstructured': 'Parris GE. Hypothesis links emergence of chloroquine-resistant malaria ' 'and other intracellular pathogens and suggests a new strategy for ' 'treatment of diseases caused by intracellular parasites. Med Hypotheses. ' '2004;62(3):354–7.', 'journal-title': 'Med Hypotheses'}, { 'key': '695_CR33', 'doi-asserted-by': 'publisher', 'first-page': '1255', 'DOI': '10.1210/clinem/dgab067', 'volume': '106', 'author': 'J Wang', 'year': '2021', 'unstructured': 'Wang J, Cooper JM, Gokhale K, Acosta-Mena D, Dhalla S, Byne N, et al. ' 'Association of metformin with susceptibility to COVID-19 in people with ' 'Type 2 diabetes. J Clin Endocrinol Metab. 2021;106:1255–68.', 'journal-title': 'J Clin Endocrinol Metab'}, { 'key': '695_CR34', 'doi-asserted-by': 'publisher', 'first-page': '119371', 'DOI': '10.1016/j.lfs.2021.119371', 'volume': '275', 'author': 'X Cheng', 'year': '2021', 'unstructured': 'Cheng X, Xin S, Chen Y, Li L, Chen W, Li W, et al. Effects of metformin, ' 'insulin on COVID-19 patients with pre-existed type 2 diabetes: a ' 'multicentral retrospective study. Life Sci. 2021;275:119371.', 'journal-title': 'Life Sci.'}, { 'key': '695_CR35', 'doi-asserted-by': 'publisher', 'first-page': '108619', 'DOI': '10.1016/j.diabres.2020.108619', 'volume': '173', 'author': 'N Jiang', 'year': '2020', 'unstructured': 'Jiang N, Chen Z, Yin X, Liu L, Yang H, Tan X, 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. ' '2020;173:108619.', 'journal-title': 'Diabetes Res Clin Pract.'}, { 'key': '695_CR36', 'doi-asserted-by': 'crossref', 'unstructured': 'Cariou B, Hadjadj S, Wargny M, Pichelin M, Gourdy P. Comment on Chen et ' 'al. Clinical characteristics and outcomes of patients with diabetes and ' 'COVID-19 in association with glucose-lowering medication. Diabetes Care ' '2020;43:1399-1407. Diabetes Care. 2020;43(10):1634-4.', 'DOI': '10.2337/dc20-1205'}, { 'issue': '1', 'key': '695_CR37', 'doi-asserted-by': 'publisher', 'first-page': '159', 'DOI': '10.1016/j.dsx.2020.12.026', 'volume': '15', 'author': 'AK Singh', 'year': '2020', 'unstructured': 'Singh AK, Singh R, Saboo B, Misra A. Non-insulin anti-diabetic agents in ' 'patients with type 2 diabetes and COVID-19: a critical appraisal of ' 'literature. Diabetes Metab Syndr. 2020;15(1):159–67.', 'journal-title': 'Diabetes Metab Syndr'}, { 'issue': '6', 'key': '695_CR38', 'doi-asserted-by': 'publisher', 'first-page': '2177', 'DOI': '10.1016/j.dsx.2020.11.006', 'volume': '14', 'author': 'AA Lukito', 'year': '2020', 'unstructured': 'Lukito AA, Pranata R, Henrina J, Lim MA, Lawrensia S, Suastika K. The ' 'Effect of Metformin Consumption on Mortality in Hospitalized COVID-19 ' 'patients: a systematic review and meta-analysis. Diabetes Metab Syndr. ' '2020;14(6):2177–83.', 'journal-title': 'Diabetes Metab Syndr'}, { 'key': '695_CR39', 'doi-asserted-by': 'publisher', 'first-page': '4273', 'DOI': '10.1002/jmv.26873', 'volume': '93', 'author': 'CT Bramante', 'year': '2021', 'unstructured': 'Bramante CT, Buse J, Tamaritz L, Palacio A, Cohen K, Vojta D, et al. ' 'Outpatient metformin use is associated with reduced severity of COVID-19 ' 'disease in adults with overweight or obesity. J Med Virol. ' '2021;93:4273–79.', 'journal-title': 'J Med Virol'}, { 'issue': '3', 'key': '695_CR40', 'doi-asserted-by': 'publisher', 'first-page': '284', 'DOI': '10.1016/j.pcd.2018.02.004', 'volume': '12', 'author': 'AA El-Arabey', 'year': '2018', 'unstructured': 'El-Arabey AA. Update on off label use of metformin for obesity. Prim ' 'Care Diabetes. 2018;12(3):284–5.', 'journal-title': 'Prim Care Diabetes'}, { 'issue': '1', 'key': '695_CR41', 'doi-asserted-by': 'publisher', 'first-page': '1', 'DOI': '10.15171/apb.2019.001', 'volume': '9', 'author': 'AA El-Arabey', 'year': '2019', 'unstructured': 'El-Arabey AA, Abdalla M, Ali EW. Metformin: ongoing journey with ' 'superdrug revolution. Adv Pharm Bull. 2019;9(1):1–4.', 'journal-title': 'Adv Pharm Bull'}, { 'key': '695_CR42', 'doi-asserted-by': 'publisher', 'first-page': '108268', 'DOI': '10.1016/j.diabres.2020.108268', 'volume': '165', 'author': 'AK Singh', 'year': '2020', 'unstructured': 'Singh AK, Singh R. Is metformin ahead in the race as a repurposed ' 'host-directed therapy for patients with diabetes and COVID-19? Diabetes ' 'Res Clin Pract. 2020;165:108268.', 'journal-title': 'Diabetes Res Clin Pract.'}, { 'issue': '10', 'key': '695_CR43', 'doi-asserted-by': 'publisher', 'first-page': '8760', 'DOI': '10.18632/aging.103347', 'volume': '12', 'author': 'JA Menendez', 'year': '2020', 'unstructured': 'Menendez JA. Metformin and SARS-CoV-2: mechanistic lessons on air ' 'pollution to weather the cytokine/thrombotic storm in COVID-19. Aging ' '(Albany NY). 2020;12(10):8760–5.', 'journal-title': 'Aging (Albany NY)'}, { 'issue': '12', 'key': '695_CR44', 'doi-asserted-by': 'publisher', 'first-page': '107723', 'DOI': '10.1016/j.jdiacomp.2020.107723', 'volume': '34', 'author': 'N Katsiki', 'year': '2020', 'unstructured': 'Katsiki N, Ferrannini E. Anti-inflammatory properties of antidiabetic ' 'drugs: a “promised land” in the COVID-19 era? J Diabetes Complications. ' '2020;34(12):107723.', 'journal-title': 'J Diabetes Complications.'}, { 'key': '695_CR45', 'doi-asserted-by': 'publisher', 'first-page': '1093', 'DOI': '10.1007/s11357-020-00261-6', 'volume': '43', 'author': 'JN Justice', 'year': '2020', 'unstructured': 'Justice JN, Gubbi S, Kulkarni AS, Bartley JM, Kuchel GA, Barzilai N. A ' 'geroscience perspective on immune resilience and infectious diseases: a ' 'potential case for metformin. 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Late treatment
is less effective
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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