Outcome and death risk of diabetes patients with Covid-19 receiving pre-hospital and in-hospital metformin therapies
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.
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Abu-Farha, Al-Mulla, Thanaraj, Kavalakatt, Ali et al., Impact of diabetes in patients diagnosed with COVID-19, Front Immunol
Apicella, Campopiano, Mantuano, Mazoni, Coppelli et al., COVID-19 in people with diabetes: understanding the reasons for worse outcomes, Lancet Diabetes Endocrinol
Bornstein, Rubino, Khunti, Mingrone, Hopkins et al., Practical recommendations for the management of diabetes in patients with COVID-19, Lancet Diabetes Endocrinol
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
Cariou, Hadjadj, Wargny, Pichelin, Al-Salameh et al., Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study, Diabetologia
Cariou, Hadjadj, Wargny, Pichelin, Gourdy et al., Clinical characteristics and outcomes of patients with diabetes and COVID-19 in association with glucose-lowering medication, Diabetes Care
Ceriello, Hyperglycemia and the worse prognosis of COVID-19. Why a fast blood glucose control should be mandatory, Diabetes Res Clin Pract
Cernigliaro, Allotta, Scondotto, Can diabetes and its related hypoglycemic drug treatment be considered risk factors for health outcomes in COVID-19 patients? The results of a study in the population residing in Sicily Region (Southern Italy), Epidemiol Prev
Chen, Yang, Cheng, Chen, Peng et al., Clinical characteristics and outcomes of patients with diabetes and COVID-19 in association with glucose-lowering medication, Diabetes Care
Cheng, Liu, Li, Zhang, Lei 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
Cheng, Xin, Chen, Li, Li, Effects of metformin, insulin on COVID-19 patients with pre-existed type 2 diabetes: a multicentral retrospective study, Life Sci
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
El-Arabey, Abdalla, Metformin and COVID-19: a novel deal of an old drug, J Med Virol
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
Ho, Petermann-Rocha, Gray, Jani, Katikireddi 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
Iacobellis, Penaherrera, Bermudez, Mizrachi, Admission hyperglycemia and radiological findings of SARS-COv2 in patients with and without diabetes, Diabetes Res Clin Pract
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
Jordaan, Dumotier, Traebert, Miller, Ghetti et al., Cardiotoxic potential of hydroxychloroquine, chloroquine and azithromycin in adult human primary cardiomyocytes, Toxicol Sci
Knopp, Miles, Webb, Mcloughlin, Mannan et al., Presenting features of COVID-19 in older people: relationships with frailty, inflammation and mortality, Eur Geriatr Med
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
Liao, Zheng, Zheng, Lu, Chao, Novel molecular evidence related to COVID-19 in patients with diabetes mellitus, J Clin Med
Lukito, Pranata, Henrina, Lim, Lawrensia et al., The Effect of Metformin Consumption on Mortality in Hospitalized COVID-19
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
Means, Mechanisms of increased morbidity and mortality of SARS-CoV-2 infection in individuals with diabetes: what this means for an effective management strategy, Metabolism
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
O'connell, Bradley, Abbas, Williamson, Rusia et al., Hydroxychloroquine/azithromycin therapy and QT prolongation in hospitalized patients with COVID-19, JACC Clin Electrophysiol
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
Parris, 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
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
Shestakova, Vikulova, Isakovmcapital, Dedov, Diabetes and COVID-19: analysis of the clinical outcomes according to the data of the Russian diabetes registry, Probl Endokrinol (Mosk)
Simabuco, Tamura, Pavan, Morale, Ventura, Molecular mechanisms and pharmacological interventions in the replication cycle of human coronaviruses, Genet Mol Biol
Singh, Ryan, Kredo, Chaplin, Fletcher, Chloroquine or hydroxychloroquine for prevention and treatment of COVID-19, Cochrane Database Syst Rev
Singh, Singh, Saboo, Misra, Non-insulin anti-diabetic agents in patients with type 2 diabetes and COVID-19: a critical appraisal of literature, Diabetes Metab Syndr
Vita, Scotti, Cammarota, Racca, Pissaia et al., Predictors of intubation in COVID-19 patients treated with out-of-ICU continuous positive airway pressure, Pulmonology, doi:10.1016/j.pulmoe.2020.12.010
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
Wargny, Potier, Gourdy, Pichelin, Amadou et al., Predictors of hospital discharge and mortality in patients with diabetes and COVID-19: updated results from the nationwide CORONADO study, Diabetologia
Wu, Mcgoogan, Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the chinese center for disease control and prevention, JAMA
Yan, Yang, Wang, Ren, Zhang et al., Clinical characteristics and outcomes of patients with severe covid-19 with diabetes, BMJ Open Diabetes Res Care