Effects of Metformin on COVID-19 Patients with Type 2 Diabetes: A Retrospective Study
Ziyu Guo, Yanxiang Gao, Enmin Xie, Zixiang Ye, Yike Li, Xuecheng Zhao, Nan Shen, Jingang Zheng
Diabetes, Metabolic Syndrome and Obesity, doi:10.2147/dmso.s417925
The pandemic of coronavirus disease 2019 (COVID-19) has highlighted the intricate relationship between underlying conditions and death. We designed this study to determine whether metformin therapy for type 2 diabetes mellitus (T2D) is associated with low in-hospital mortality in patients hospitalized for COVID-19. Materials and Methods: This was a retrospective study including patients with COVID-19 and T2D in Wuhan, from February 4th to April 11th, 2020. Patients were divided into two groups according to metformin exposure. The hazard ratio (HR) of COVID-19-related mortality and invasive mechanical ventilation was estimated using Cox regression. Results: There were 571 T2D patients among the 4330 confirmed COVID-19 patients. Of those patients, 241 received metformin therapy. The in-hospital mortality and invasive mechanical ventilation of metformin group was lower than non-metformin group. In the multivariate model, metformin use was linked to a decreased in-hospital mortality and invasive mechanical ventilation when compared with that of the control group (HR: 0.376 [95% CI 0.154-0.922]; P = 0.033).
Conclusion: Our study indicated that metformin therapy was associated with decreased death risk in COVID-19 patients with T2D.
Abbreviations T2D, type 2 diabetes mellitus; COVID-19, coronavirus disease 2019; HR, hazard ratio; SARA-COV-2, severe acute respiratory syndrome coronavirus 2; ACE2, angiotensin-converting enzyme 2; AMPK, 5'-AMP-activated protein kinase; DPP4, dipeptidyl peptidase-4; CK-MB, creatine kinase-myocardial band; ALT, alanine aminotransferase; LDH, lactic https://doi.org/10.2147/DMSO.S417925
DovePress Diabetes, Metabolic Syndrome and Obesity 2023:16
Disclosure The authors declare that they have no known competing commercial or financial relationships that could have appeared to influence the work reported in this paper.
References
Apicella, Campopiano, Mantuano, COVID-19 in people with diabetes: understanding the reasons for worse outcomes, Lancet Diabetes Endocrinol,
doi:10.1016/S2213-8587(20)30238-2Bornstein, Rubino, Khunti, Practical recommendations for the management of diabetes in patients with COVID-19, Lancet Diabetes Endocrinol,
doi:10.1016/S2213-8587(20)30152-2Bramante, Huling, Tignanelli, Randomized trial of metformin, ivermectin, and fluvoxamine for Covid-19, N Engl J Med,
doi:10.1056/NEJMoa2201662Bramante, The COVID-OUT study: a randomized, double-blind, placebo-controlled trial of metformin for the treatment of COVID-19 sequelae
Cariou, Hadjadj, Wargny, Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study, Diabetologia,
doi:10.1007/s00125-020-05180-xCeriello, Hyperglycemia and the worse prognosis of COVID-19. Why a fast blood glucose control should be mandatory, Diabetes Res Clin Pract,
doi:10.1016/j.diabres.2020.108186Cheng, Liu, Li, 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.2020.08.013Crouse, Grimes, Li, Metformin use is associated with reduced mortality in a diverse population with COVID-19 and diabetes, Front Endocrinol,
doi:10.3389/fendo.2020.600439Hashemi, Pezeshki, Repurposing metformin for covid-19 complications in patients with type 2 diabetes and insulin resistance, Immunopharmacol Immunotoxicol,
doi:10.1080/08923973.2021.1925294Iacobellis, Penaherrera, Bermudez, Admission hyperglycemia and radiological findings of SARS-CoV2 in patients with and without diabetes, Diabetes Res Clin Pract,
doi:10.1016/j.diabres.2020.108185Nguyen, Ho, Nguyen, Preadmission use of antidiabetic medications and mortality among patients with COVID-19 having type 2 diabetes: a meta-analysis, Metabolism,
doi:10.1016/j.metabol.2022.155196Richardson, Hirsch, Narasimhan, Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area, JAMA,
doi:10.1001/jama.2020.6775Roca-Ho, Riera, Palau, Characterization of ACE and ACE2 expression within different organs of the NOD mouse, Int J Mol Sci,
doi:10.3390/ijms18030563Sancho-López, Caballero-Bermejo, Ruiz-Antorán, Efficacy and safety of sarilumab in patients with COVID19 pneumonia: a randomized, phase III clinical trial (SARTRE study), Infect Dis Ther
Singh, Khunti, Assessment of risk, severity, mortality, glycemic control and antidiabetic agents in patients with diabetes and COVID-19: a narrative review, Diabetes Res Clin Pract,
doi:10.1016/j.diabres.2020.108266Wang, Cooper, Gokhale, Association of metformin with susceptibility to COVID-19 in people with type 2 diabetes, J Clin Endocrinol Metab,
doi:10.1210/clinem/dgab067Yu, Li, Sun, Insulin treatment is associated with increased mortality in patients with COVID-19 and type 2 diabetes, Cell Metab,
doi:10.1016/j.cmet.2020.11.014Zhang, Dong, Martin, AMP-activated protein kinase phosphorylation of angiotensin-converting enzyme 2 in endothelium mitigates pulmonary hypertension, Am J Respir Crit Care Med,
doi:10.1164/rccm.201712-2570OCZhang, Qin, Cheng, In-hospital use of statins is associated with a reduced risk of mortality among individuals with COVID-19, Cell Metab,
doi:10.1016/j.cmet.2020.06.015Zhu, She, Cheng, Association of blood glucose control and outcomes in patients with COVID-19 and pre-existing type 2 diabetes, Cell Metab,
doi:10.1016/j.cmet.2020.04.021{ 'indexed': {'date-parts': [[2023, 8, 24]], 'date-time': '2023-08-24T04:24:26Z', 'timestamp': 1692851066943},
'reference-count': 25,
'publisher': 'Informa UK Limited',
'license': [ { 'start': { 'date-parts': [[2023, 8, 1]],
'date-time': '2023-08-01T00:00:00Z',
'timestamp': 1690848000000},
'content-version': 'unspecified',
'delay-in-days': 0,
'URL': 'https://creativecommons.org/licenses/by-nc/3.0/'}],
'content-domain': {'domain': [], 'crossmark-restriction': False},
'DOI': '10.2147/dmso.s417925',
'type': 'journal-article',
'created': {'date-parts': [[2023, 8, 24]], 'date-time': '2023-08-24T02:00:12Z', 'timestamp': 1692842412000},
'page': '2573-2582',
'source': 'Crossref',
'is-referenced-by-count': 0,
'title': 'Effects of Metformin on COVID-19 Patients with Type 2 Diabetes: A Retrospective Study',
'prefix': '10.2147',
'volume': 'Volume 16',
'author': [ {'given': 'Ziyu', 'family': 'Guo', 'sequence': 'first', 'affiliation': []},
{'given': 'Yanxiang', 'family': 'Gao', 'sequence': 'additional', 'affiliation': []},
{'given': 'Enmin', 'family': 'Xie', 'sequence': 'additional', 'affiliation': []},
{'given': 'Zixiang', 'family': 'Ye', 'sequence': 'additional', 'affiliation': []},
{'given': 'Yike', 'family': 'Li', 'sequence': 'additional', 'affiliation': []},
{'given': 'Xuecheng', 'family': 'Zhao', 'sequence': 'additional', 'affiliation': []},
{'given': 'Nan', 'family': 'Shen', 'sequence': 'additional', 'affiliation': []},
{'given': 'Jingang', 'family': 'Zheng', 'sequence': 'additional', 'affiliation': []}],
'member': '301',
'published-online': {'date-parts': [[2023, 8]]},
'reference': [ { 'key': 'ref1',
'doi-asserted-by': 'publisher',
'first-page': '782',
'DOI': '10.1016/S2213-8587(20)30238-2',
'volume': '8',
'author': 'Apicella',
'year': '2020',
'journal-title': 'Lancet Diabetes Endocrinol'},
{ 'key': 'ref2',
'doi-asserted-by': 'publisher',
'first-page': '2052',
'DOI': '10.1001/jama.2020.6775',
'volume': '323',
'author': 'Richardson',
'year': '2020',
'journal-title': 'JAMA'},
{ 'key': 'ref3',
'doi-asserted-by': 'publisher',
'first-page': '1068',
'DOI': '10.1016/j.cmet.2020.04.021',
'volume': '31',
'author': 'Zhu',
'year': '2020',
'journal-title': 'Cell Metab'},
{ 'key': 'ref4',
'doi-asserted-by': 'publisher',
'first-page': '335',
'DOI': '10.1016/j.diabet.2020.05.001',
'volume': '46',
'author': 'Targher',
'year': '2020',
'journal-title': 'Diabetes Metab'},
{ 'key': 'ref5',
'doi-asserted-by': 'publisher',
'first-page': '108266',
'DOI': '10.1016/j.diabres.2020.108266',
'volume': '165',
'author': 'Singh',
'year': '2020',
'journal-title': 'Diabetes Res Clin Pract'},
{ 'key': 'ref6',
'doi-asserted-by': 'publisher',
'first-page': '221',
'DOI': '10.1007/s00125-019-05039-w',
'volume': '63',
'author': 'Buse',
'year': '2020',
'journal-title': 'Diabetologia'},
{ 'key': 'ref7',
'doi-asserted-by': 'publisher',
'first-page': '537',
'DOI': '10.1016/j.cmet.2020.08.013',
'volume': '32',
'author': 'Cheng',
'year': '2020',
'journal-title': 'Cell Metab'},
{ 'key': 'ref8',
'doi-asserted-by': 'publisher',
'first-page': '265',
'DOI': '10.1080/08923973.2021.1925294',
'volume': '43',
'author': 'Hashemi',
'year': '2021',
'journal-title': 'Immunopharmacol Immunotoxicol'},
{ 'key': 'ref9',
'doi-asserted-by': 'publisher',
'first-page': '108183',
'DOI': '10.1016/j.diabres.2020.108183',
'volume': '164',
'author': 'Sharma',
'year': '2020',
'journal-title': 'Diabetes Res Clin Pract'},
{ 'key': 'ref10',
'doi-asserted-by': 'publisher',
'first-page': '509',
'DOI': '10.1164/rccm.201712-2570OC',
'volume': '198',
'author': 'Zhang',
'year': '2018',
'journal-title': 'Am J Respir Crit Care Med'},
{ 'key': 'ref11',
'unstructured': 'Bramante C. The COVID-OUT study: a randomized, double-blind, '
'placebo-controlled trial of metformin for the treatment of COVID-19 '
'sequelae. medRxiv; 2021.'},
{ 'key': 'ref12',
'doi-asserted-by': 'publisher',
'first-page': '65',
'DOI': '10.1016/j.cmet.2020.11.014',
'volume': '33',
'author': 'Yu',
'year': '2021',
'journal-title': 'Cell Metab'},
{ 'key': 'ref13',
'first-page': '1',
'volume': '2021',
'author': 'Sancho-López',
'year': '2021',
'journal-title': 'Infect Dis Ther'},
{ 'key': 'ref14',
'doi-asserted-by': 'publisher',
'first-page': '176',
'DOI': '10.1016/j.cmet.2020.06.015',
'volume': '32',
'author': 'Zhang',
'year': '2020',
'journal-title': 'Cell Metab'},
{ 'key': 'ref15',
'doi-asserted-by': 'publisher',
'first-page': '1225',
'DOI': '10.1016/S0140-6736(20)30627-9',
'volume': '395',
'author': 'Remuzzi',
'year': '2020',
'journal-title': 'Lancet'},
{ 'key': 'ref16',
'doi-asserted-by': 'publisher',
'first-page': '108185',
'DOI': '10.1016/j.diabres.2020.108185',
'volume': '164',
'author': 'Iacobellis',
'year': '2020',
'journal-title': 'Diabetes Res Clin Pract'},
{ 'key': 'ref17',
'doi-asserted-by': 'publisher',
'first-page': '546',
'DOI': '10.1016/S2213-8587(20)30152-2',
'volume': '8',
'author': 'Bornstein',
'year': '2020',
'journal-title': 'Lancet Diabetes Endocrinol'},
{ 'key': 'ref18',
'doi-asserted-by': 'publisher',
'first-page': '1500',
'DOI': '10.1007/s00125-020-05180-x',
'volume': '63',
'author': 'Cariou',
'year': '2020',
'journal-title': 'Diabetologia'},
{ 'key': 'ref19',
'doi-asserted-by': 'publisher',
'first-page': '600439',
'DOI': '10.3389/fendo.2020.600439',
'volume': '11',
'author': 'Crouse',
'year': '2020',
'journal-title': 'Front Endocrinol'},
{ 'key': 'ref20',
'doi-asserted-by': 'publisher',
'first-page': '155196',
'DOI': '10.1016/j.metabol.2022.155196',
'volume': '131',
'author': 'Nguyen',
'year': '2022',
'journal-title': 'Metabolism'},
{ 'key': 'ref21',
'doi-asserted-by': 'publisher',
'first-page': '1255',
'DOI': '10.1210/clinem/dgab067',
'volume': '106',
'author': 'Wang',
'year': '2021',
'journal-title': 'J Clin Endocrinol Metab'},
{ 'key': 'ref22',
'doi-asserted-by': 'publisher',
'first-page': '599',
'DOI': '10.1056/NEJMoa2201662',
'volume': '387',
'author': 'Bramante',
'year': '2022',
'journal-title': 'N Engl J Med'},
{ 'key': 'ref23',
'doi-asserted-by': 'publisher',
'first-page': '108186',
'DOI': '10.1016/j.diabres.2020.108186',
'volume': '163',
'author': 'Ceriello',
'year': '2020',
'journal-title': 'Diabetes Res Clin Pract'},
{ 'key': 'ref24',
'doi-asserted-by': 'publisher',
'first-page': '563',
'DOI': '10.3390/ijms18030563',
'volume': '18',
'author': 'Roca-Ho',
'year': '2017',
'journal-title': 'Int J Mol Sci'},
{ 'key': 'ref25',
'doi-asserted-by': 'publisher',
'first-page': '108167',
'DOI': '10.1016/j.diabres.2020.108167',
'volume': '164',
'author': 'Ursini',
'year': '2020',
'journal-title': 'Diabetes Res Clin Pract'}],
'container-title': 'Diabetes, Metabolic Syndrome and Obesity',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://www.dovepress.com/getfile.php?fileID=92248',
'content-type': 'application/pdf',
'content-version': 'vor',
'intended-application': 'text-mining'},
{ 'URL': 'https://www.dovepress.com/getfile.php?fileID=92248',
'content-type': 'application/pdf',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2023, 8, 24]],
'date-time': '2023-08-24T02:00:17Z',
'timestamp': 1692842417000},
'score': 1,
'resource': { 'primary': { 'URL': 'https://www.dovepress.com/effects-of-metformin-on-covid-19-patients-with-type-2-diabetes-a-retro-peer-reviewed-fulltext-article-DMSO'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2023, 8]]},
'references-count': 25,
'URL': 'http://dx.doi.org/10.2147/DMSO.S417925',
'relation': {},
'ISSN': ['1178-7007'],
'subject': ['Pharmacology', 'Internal Medicine'],
'container-title-short': 'DMSO',
'published': {'date-parts': [[2023, 8]]}}
