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0 0.5 1 1.5 2+ Mortality 1% Improvement Relative Risk Metformin  Ramos-Rincón et al.  Prophylaxis Is prophylaxis with metformin beneficial for COVID-19? Retrospective 790 patients in Spain (March - May 2020) No significant difference in mortality c19early.org Ramos-Rincón et al., Research Square, Dec 2020 Favors metformin Favors control

Association between prior cardiometabolic therapy and in-hospital mortality in very old patients with type 2 diabetes mellitus hospitalized due to COVID-19. A nationwide observational study in Spain

Ramos-Rincón et al., Research Square, doi:10.21203/rs.3.rs-133358/v1
Dec 2020  
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Metformin for COVID-19
3rd treatment shown to reduce risk in July 2020
 
*, now known with p < 0.00000000001 from 89 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. c19early.org
Retrospective 790 hospitalized type 2 diabetes patients ≥80 years old in Spain, showing no significant difference in mortality with existing metformin use.
Study covers aspirin and metformin.
risk of death, 1.3% lower, RR 0.99, p = 0.78, treatment 206 of 420 (49.0%), control 179 of 370 (48.4%), adjusted per study, odds ratio converted to relative risk, multivariable.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Ramos-Rincón et al., 28 Dec 2020, retrospective, Spain, preprint, 25 authors, study period 1 March, 2020 - 29 May, 2020. Contact: luismiguelpb1984@gmail.com.
This PaperMetforminAll
Association between prior cardiometabolic therapy and in-hospital mortality in very old patients with type 2 diabetes mellitus hospitalized due to COVID-19. A nationwide observational study in Spain
Jose Manuel Ramos-Rincón, Luis M Pérez-Belmonte, Francisco Javier Carrasco-Sánchez, Sergio Jansen-Chaparro, Mercedes De-Sousa-Baena, José Bueno-Fonseca, Maria Pérez-Aguilar, Coral Arévalo Cañas, Marta Bacete Cebrian, Manuel Méndez-Bailón, Isabel Fiteni Mera, Andrés González García, Francisco Navarro Romero, Carlota Tuñón De Almeida, Gemma Muñiz Nicolás, Amara González Noya, Almudena Hernández Milian, Gema María García García, José Nicolás Alcalá Pedrajas, Virginia Herrero García, Luis Corral-Gudino, Pere Comas Casanova, Héctor Meijide Míguez, José Manuel Casas-Rojo, Ricardo Gómez-Huelgas
doi:10.21203/rs.3.rs-133358/v1
Background Advanced age and diabetes are both associated with poor prognosis in COVID-19. However, the effects of cardiometabolic drugs on the prognosis of diabetic patients with COVID-19, especially very old patients, are not well-known. This work aims to analyze the association between preadmission cardiometabolic therapy (antidiabetic, antiaggregant, antihypertensive, and lipid-lowering drugs) and in-hospital mortality among patients ≥ 80 years with type 2 diabetes mellitus hospitalized for COVID-19. Methods We conducted a nationwide, multicenter, retrospective, observational study in patients ≥ 80 years with type 2 diabetes mellitus and COVID-19 hospitalized in 160 Spanish hospitals between March 1 and May 29, 2020 who were included in the SEMI-COVID-19 Registry. The primary outcome measure was inhospital mortality. A multivariate logistic regression analysis were performed to assess the association between preadmission cardiometabolic therapy and in-hospital mortality. The regression analysis values were expressed as adjusted odds ratios (AOR) with a 95% con dence interval (CI). In order to select the variables, the forward selection Wald statistic was used. Discrimination of the tted logistic model was assessed via a receiver operating characteristic (ROC) curve. The Hosmer-Lemeshow test for logistic regression was used to determine the model's goodness of t.
Declarations Ethics approval and consent to participate gave their informed consent. When there were biosafety concerns and/or when the patient had already been discharged, verbal informed consent was requested and noted on the medical record. Data con dentiality and patient anonymity were maintained at all times, in accordance with Spanish regulations on observational studies. This study was carried out in accordance with the Declaration of Helsinki and was approved by the Institutional Research Ethics Committee of Málaga on March 27, 2020 (Ethics Committe code: SEMI-COVID-19 27-03-20), as per the guidelines of the Spanish Agency of Medicines and Medical Products. Consent for publication Not applicable. Competing interest The authors declare that they have no competing interests. Authors' contributions JMRR contributed to the conception, design of the work the acquisition, interpretation of data, writingoriginal draft preparation, writing-review and editing, and supervision. FJCS, SJC, MDSB, JBF, MPA, CAC, MBC, MMB, IFM, AGG, FNR, CTA, GMN, AGN, AHM, GMGG, JNAP, VHG, LCG, PCC, HMM, and JMCR made contributions to the acquisition of data and revised the work. LMPB contributed to interpretation of data, writing-review and editing, and supervision. RGH was a major contributor in interpretation of data, writingoriginal draft preparation, writing-review and editing, and supervision. All authors read and approved the nal manuscript. Supplementary Files This is a list of..
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{ 'DOI': '10.21203/rs.3.rs-133358/v1', 'URL': 'http://dx.doi.org/10.21203/rs.3.rs-133358/v1', 'abstract': '<jats:title>Abstract</jats:title>\n' ' <jats:p>Background\n' '\n' 'Advanced age and diabetes are both associated with poor prognosis in COVID-19. However, the ' 'effects of cardiometabolic drugs on the prognosis of diabetic patients with COVID-19, ' 'especially very old patients, are not well-known. This work aims to analyze the association ' 'between preadmission cardiometabolic therapy (antidiabetic, antiaggregant, antihypertensive, ' 'and lipid-lowering drugs) and in-hospital mortality among patients\u2009≥\u200980 years with ' 'type 2 diabetes mellitus hospitalized for COVID-19.\n' 'Methods\n' '\n' 'We conducted a nationwide, multicenter, retrospective, observational study in patients\u2009' '≥\u200980 years with type 2 diabetes mellitus and COVID-19 hospitalized in 160 Spanish ' 'hospitals between March 1 and May 29, 2020 who were included in the SEMI-COVID-19 Registry. ' 'The primary outcome measure was in-hospital mortality. A multivariate logistic regression ' 'analysis were performed to assess the association between preadmission cardiometabolic ' 'therapy and in-hospital mortality. The regression analysis values were expressed as adjusted ' 'odds ratios (AOR) with a 95% confidence interval (CI). In order to select the variables, the ' 'forward selection Wald statistic was used. Discrimination of the fitted logistic model was ' 'assessed via a receiver operating characteristic (ROC) curve. The Hosmer-Lemeshow test for ' 'logistic regression was used to determine the model’s goodness of fit.\n' 'Results\n' '\n' 'Of the 2,763 patients ≥80 years old hospitalized due to COVID-19, 790 (28.6%) had T2DM. Of ' 'these patients, 385 (48.7%) died during admission. On the multivariate analysis, the use of ' 'dipeptidyl peptidase-4 inhibitors (AOR 0.502, 95% CI 0.309–0.815, p\u2009=\u20090.005) and ' 'angiotensin receptor blockers (AOR 0.454, 95% CI 0.274–0.759, p\u2009=\u20090.003) were ' 'independent protectors against in-hospital mortality whereas the use of acetylsalicylic acid ' 'was associated with higher in-hospital mortality (AOR 1.761, 95% CI 1.092–2.842, p\u2009' '=\u20090.020). Other antidiabetic drugs, angiotensin-converting enzyme inhibitors and statins ' 'showed neutral association with in-hospital mortality. The model showed an area under the ' 'curve of 0.788.\n' 'Conclusions\n' '\n' 'We found important differences between cardiometabolic drugs and in-hospital mortality in ' 'older patients with type 2 diabetes mellitus hospitalized for COVID-19. Preadmission ' 'treatment with dipeptidyl peptidase-4 inhibitors and angiotensin receptor blockers may reduce ' 'in-hospital mortality; other antidiabetic drugs, angiotensin-converting enzyme inhibitors and ' 'statins seem to have a neutral effect; and acetylsalicylic acid may be associated with excess ' 'mortality.</jats:p>', 'accepted': {'date-parts': [[2020, 12, 21]]}, 'author': [ { 'affiliation': [ { 'name': 'Miguel Hernandez University of Elche: Universidad Miguel ' 'Hernandez de Elche'}], 'family': 'Ramos-Rincón', 'given': 'Jose Manuel', 'sequence': 'first'}, { 'ORCID': 'http://orcid.org/0000-0001-9512-8274', 'affiliation': [ { 'name': 'Hospital Regional Universitario de Málaga: Hospital Regional ' 'Universitario de Malaga'}], 'authenticated-orcid': False, 'family': 'Pérez-Belmonte', 'given': 'Luis M', 'sequence': 'additional'}, { 'affiliation': [{'name': 'Hospital Juan Ramón Jiménez: Hospital Juan Ramon Jimenez'}], 'family': 'Carrasco-Sánchez', 'given': 'Francisco Javier', 'sequence': 'additional'}, { 'affiliation': [ { 'name': 'Hospital Regional Universitario de Málaga: Hospital Regional ' 'Universitario de Malaga'}], 'family': 'Jansen-Chaparro', 'given': 'Sergio', 'sequence': 'additional'}, { 'affiliation': [{'name': 'Hospital Juan Ramón Jiménez: Hospital Juan Ramon Jimenez'}], 'family': 'De-Sousa-Baena', 'given': 'Mercedes', 'sequence': 'additional'}, { 'affiliation': [ { 'name': 'Hospital Regional Universitario de Málaga: Hospital Regional ' 'Universitario de Malaga'}], 'family': 'Bueno-Fonseca', 'given': 'José', 'sequence': 'additional'}, { 'affiliation': [{'name': 'Hospital Juan Ramón Jiménez: Hospital Juan Ramon Jimenez'}], 'family': 'Pérez-Aguilar', 'given': 'Maria', 'sequence': 'additional'}, { 'affiliation': [{'name': 'Hospital 12 de Octubre Servicio de Medicina Interna'}], 'family': 'Cañas', 'given': 'Coral Arévalo', 'sequence': 'additional'}, { 'affiliation': [ { 'name': 'Hospital General Universitario Gregorio Marañón: Hospital ' 'General Universitario Gregorio Maranon'}], 'family': 'Cebrian', 'given': 'Marta Bacete', 'sequence': 'additional'}, { 'affiliation': [ { 'name': 'San Carlos University Hospital Internal Medicine III Service: ' 'Hospital Clinico Universitario San Carlos Servicio de Medicina ' 'Interna III'}], 'family': 'Méndez-Bailón', 'given': 'Manuel', 'sequence': 'additional'}, { 'affiliation': [{'name': 'Royo Villanova Hospital: Hospital Royo Villanova'}], 'family': 'Mera', 'given': 'Isabel Fiteni', 'sequence': 'additional'}, { 'affiliation': [{'name': 'Hospital Ramon y Cajal: Hospital Universitario Ramon y Cajal'}], 'family': 'García', 'given': 'Andrés González', 'sequence': 'additional'}, { 'affiliation': [{'name': 'Hospital Costa del Sol'}], 'family': 'Romero', 'given': 'Francisco Navarro', 'sequence': 'additional'}, { 'affiliation': [{'name': ': Complejo Asistencial de Zamora'}], 'family': 'Almeida', 'given': 'Carlota Tuñón de', 'sequence': 'additional'}, { 'affiliation': [{'name': 'Hospital Virgen de la Salud'}], 'family': 'Nicolás', 'given': 'Gemma Muñiz', 'sequence': 'additional'}, { 'affiliation': [ { 'name': 'Complejo Hospitalario de Orense: Complexo Hospitalario de ' 'Ourense'}], 'family': 'Noya', 'given': 'Amara González', 'sequence': 'additional'}, { 'affiliation': [ { 'name': 'Hospital Universitario Son Espases: Hospital Universitari Son ' 'Espases'}], 'family': 'Milian', 'given': 'Almudena Hernández', 'sequence': 'additional'}, { 'affiliation': [{'name': 'Complejo Hospitalario Universitario de Badajoz'}], 'family': 'García', 'given': 'Gema María García', 'sequence': 'additional'}, { 'affiliation': [{'name': 'VS Hospital'}], 'family': 'Pedrajas', 'given': 'José Nicolás Alcalá', 'sequence': 'additional'}, { 'affiliation': [{'name': 'Hospital Doctor Jose Molina Orosa'}], 'family': 'García', 'given': 'Virginia Herrero', 'sequence': 'additional'}, { 'affiliation': [{'name': 'Hospital Universitario Rio Hortega'}], 'family': 'Corral-Gudino', 'given': 'Luis', 'sequence': 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