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
Luis M. Pérez-Belmonte,
José David Torres-Peña,
María D. López-Carmona,
M. Mar. Ayala-Gutiérrez,
Francisco Fuentes-Jiménez,
Lucía Jorge Huerta,
Jaime Alonso Muñoz,
Manuel Rubio-Rivas,
Manel Madrazo,
Marcos Guzmán Garcia,
Beatriz Vicente Montes,
Joaquim Fernández Sola,
Javier Ena,
Ruth Gonzalez Ferrer,
Carmen Mella Pérez,
Carlos Jorge Ripper,
Jose Javier Napal Lecumberri,
Iris El Attar Acedo,
Susana Plaza Canteli,
Sara Fuente Cosío,
Francisco Amorós Martínez,
Begoña Cortés Rodríguez,
Pablo Pérez-Martínez,
José Manuel Ramos-Rincón,
Ricardo Gómez-Huelgas,
for the SEMI-COVID-19 Network
Affiliations
Luis M. Pérez-Belmonte
Internal Medicine Department, Regional University Hospital of Málaga, Biomedical Research Institute of Málaga (IBIMA), University of Málaga (UMA)
José David Torres-Peña
Lipids and Atherosclerosis Unit, Department of Internal Medicine, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba
María D. López-Carmona
Internal Medicine Department, Regional University Hospital of Málaga, Biomedical Research Institute of Málaga (IBIMA), University of Málaga (UMA)
M. Mar. Ayala-Gutiérrez
Internal Medicine Department, Regional University Hospital of Málaga, Biomedical Research Institute of Málaga (IBIMA), University of Málaga (UMA)
Francisco Fuentes-Jiménez
Lipids and Atherosclerosis Unit, Department of Internal Medicine, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba
Lucía Jorge Huerta
Internal Medicine Department, 12 de Octubre University Hospital
Jaime Alonso Muñoz
Internal Medicine Department, Gregorio Marañon University Hospital
Manuel Rubio-Rivas
Internal Medicine Department, Bellvitge University Hospital
Manel Madrazo
Internal Medicine Department, Dr. Peset University Hospital
Marcos Guzmán Garcia
Internal Medicine Department, San Juan de la Cruz Hospital
Beatriz Vicente Montes
Internal Medicine Department, León University Hospital Complex
Joaquim Fernández Sola
Internal Medicine Department, Clinic Barcelona Hospital
Javier Ena
Internal Medicine Department, Marina Baixa Hospital
Ruth Gonzalez Ferrer
Internal Medicine Department, Tajo Hospital
Carmen Mella Pérez
Internal Medicine Department, Ferrol University Hospital Complex
Carlos Jorge Ripper
Internal Medicine Department, Insular de Gran Canaria Hospital
Jose Javier Napal Lecumberri
Internal Medicine Department, Marqués de Valdecilla University Hospital
Iris El Attar Acedo
Internal Medicine Department, Torrecárdenas Hospital
Susana Plaza Canteli
Internal Medicine Department, Severo Ochoa University Hospital
Sara Fuente Cosío
Internal Medicine Department, Valle del Nalón Hospital
Francisco Amorós Martínez
Internal Medicine Department, Vinalopó University Hospital
Begoña Cortés Rodríguez
Internal Medicine Department, Alto Guadalquivir Hospital
Pablo Pérez-Martínez
Lipids and Atherosclerosis Unit, Department of Internal Medicine, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba
José Manuel Ramos-Rincón
Department of Clinical Medicine, Miguel Hernandez University of Elche
Ricardo Gómez-Huelgas
Internal Medicine Department, Regional University Hospital of Málaga, Biomedical Research Institute of Málaga (IBIMA), University of Málaga (UMA)
Abstract Background Limited evidence exists on the role of glucose-lowering drugs in patients with COVID-19. Our main objective was to examine the association between in-hospital death and each routine at-home glucose-lowering drug both individually and in combination with metformin in patients with type 2 diabetes mellitus admitted for COVID-19. We also evaluated their association with the composite outcome of the need for ICU admission, invasive and non-invasive mechanical ventilation, or in-hospital death as well as on the development of in-hospital complications and a long-time hospital stay. Methods We selected all patients with type 2 diabetes mellitus in the Spanish Society of Internal Medicine’s registry of COVID-19 patients (SEMI-COVID-19 Registry). It is an ongoing, observational, multicenter, nationwide cohort of patients admitted for COVID-19 in Spain from March 1, 2020. Each glucose-lowering drug user was matched with a user of other glucose-lowering drugs in a 1:1 manner by propensity scores. In order to assess the adequacy of propensity score matching, we used the standardized mean difference found in patient characteristics after matching. There was considered to be a significant imbalance in the group if a standardized mean difference > 10% was found. To evaluate the association between treatment and study outcomes, both conditional logit and mixed effect logistic regressions were used when the sample size was ≥ 100. Results A total of 2666 patients were found in the SEMI-COVID-19 Registry, 1297 on glucose-lowering drugs in monotherapy and 465 in combination with metformin. After propensity matching, 249 patients on metformin, 105 on dipeptidyl peptidase-4 inhibitors, 129 on insulin, 127 on metformin/dipeptidyl peptidase-4 inhibitors, 34 on metformin/sodium-glucose cotransporter 2 inhibitor, and 67 on metformin/insulin were selected. No at-home glucose-lowering drugs showed a significant association with in-hospital death; the composite outcome of the need of intensive care unit admission, mechanical ventilation, or in-hospital death; in-hospital complications; or long-time hospital stays. Conclusions In patients with type 2 diabetes mellitus admitted for COVID-19, at-home glucose-lowering drugs showed no significant association with mortality and adverse outcomes. Given the close relationship between diabetes and COVID-19 and the limited evidence on the role of glucose-lowering drugs, prospective studies are needed.