A multicenter, real-world cohort study: effectiveness and safety of Azvudine in hospitalized COVID-19 patients with pre-existing diabetes
Yongjian Zhou, Zecheng Yang, Shixi Zhang, Donghua Zhang, Hong Luo, Di Zhu, Guangming Li, Mengzhao Yang, Xiaobo Hu, Guowu Qian, Guotao Li, Ling Wang, Silin Li, Zujiang Yu, Zhigang Ren, Kedra Wallace, Amelia Caretto
doi:10.3389/fendo.2025.1467303
Introduction: During the Omicron infection wave, diabetic patients are susceptible to COVID-19, which is linked to a poor prognosis. However, research on the real-world effectiveness and safety of Azvudine, a common medication for COVID-19, is insufficient in those with pre-existing diabetes. Methods: In this retrospective study, we included 32,864 hospitalized COVID-19 patients from 9 hospitals in Henan Province. Diabetic patients were screened and divided into the Azvudine group and the control group, via 1:1 propensity score matching. The primary outcome was all-cause mortality, and the secondary outcome was composite disease progression. Laboratory abnormal results were used for safety evaluation. Results: A total of 1,417 patients receiving Azvudine and 1,417 patients receiving standard treatment were ultimately included. Kaplan-Meier curves suggested that all-cause mortality (P = 0.0026) was significantly lower in the Azvudine group than in the control group, but composite disease progression did not significantly differ (P = 0.1). Cox regression models revealed Azvudine treatment could reduce 26% risk of all-cause mortality (95% CI: 0.583-0.942, P = 0.015) versus controls, and not reduce the risk of composite disease progression (HR: 0.91, 95% CI: 0.750-1.109, P = 0.355). The results of subgroup analysis and three sensitivity analyses were consistent with the previous findings. Safety analysis revealed that the incidence rates of most adverse events were similar between the two groups.
Ethics statement The study was approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University (2023-KY-0865-001). The studies were conducted in accordance with the local legislation and institutional requirements. The ethics committee/institutional review board waived the requirement of written informed consent for participation from the participants or the participants' legal guardians/next of kin because the private information of all patients was not disclosed in this retrospective study, the Ethics Committee of the First Affiliated Hospital of Zhengzhou University approved the waiver of obtaining informed consent.
Author contributions
Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher's note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Supplementary material The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fendo.2025.1467303/ full#supplementary-material
References
Arbel, Sagy, Hoshen, Battat, Lavie et al., Nirmatrelvir use and severe covid-19 outcomes during the omicron surge, N Engl J Med,
doi:10.1056/NEJMoa2204919Bernal, Da Silva, Musungaie, Kovalchuk, Gonzalez et al., Molnupiravir for oral treatment of covid-19 in nonhospitalized patients, N Engl J Med,
doi:10.1056/NEJMoa2116044Bode, Garrett, Messler, Mcfarland, Crowe et al., Glycemic characteristics and clinical outcomes of COVID-19 patients hospitalized in the United States, J Diabetes Sci Technol,
doi:10.1177/1932296820924469Brufsky, Hyperglycemia, hydroxychloroquine, and the COVID-19 pandemic, J Med Virol,
doi:10.1002/jmv.25887Caretto, Terlizzi, Pedone, Pennella, Cobelli et al., Tight and stable glucose control is associated with better prognosis in patients hospitalized for covid-19 and pneumonia, Acta Diabetol,
doi:10.1007/s00592-024-02409-8Cariou, Hadjadj, Wargny, Pichelin, Al-Salameh et al., Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: The CORONADO study, Diabetologia,
doi:10.1007/s00125-020-05180-xCodo, Davanzo, Monteiro, De, De Souza et al., Elevated glucose levels favor SARS-CoV-2 infection and monocyte response through a HIF-1a/glycolysis-dependent axis, Cell Metab,
doi:10.1016/j.cmet.2020.07.007De Souza, Cabral, Da Silva, Arruda, Sp De et al., randomized, double-blind, placebo-controlled clinical study: A study on the safety and clinical efficacy of AZVUDINE in moderate COVID-19 patients, Front Med,
doi:10.3389/fmed.2023.1215916Garcia-Beltran, Lam, Denis, Nitido, Garcia et al., Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity, Cell,
doi:10.1016/j.cell.2021.03.013Gregory, Slaughter, Duffus, Smith, Lestourgeon et al., COVID-19 severity is tripled in the diabetes community: A prospective analysis of the pandemic's impact in type 1 and type 2 diabetes, Diabetes Care,
doi:10.2337/dc20-2260Gutieŕrez-Calderoń, Sarti, COVID-19 vaccination hesitancy in Mexico city among healthy adults and adults with chronic diseases: A survey of complacency, confidence, and convenience challenges in the transition to endemic control, Vaccines,
doi:10.3390/vaccines10111944Han, Du, Deng, Tang, Dong et al., Real-world effectiveness and safety of simnotrelvir/ritonavir for COVID-19: A nationwide, multicenter, prospective, observational cohort study in China, J Infect,
doi:10.1016/j.jinf.2024.106339Laurenzi, Caretto, Molinari, Bazzigaluppi, Brigatti et al., Pre-existing diabetes and COVID-associated hyperglycaemia in patients with COVID-19 pneumonia, Biology,
doi:10.3390/biology10080754Li, Shen, Yang, Fairley, Chai et al., Global diabetes prevalence in COVID-19 patients and contribution to COVID-19-related severity and mortality: A systematic review and meta-analysis, Diabetes Care,
doi:10.2337/dc22-1943Lim, Bae, Kwon, Nauck, COVID-19 and diabetes mellitus: From pathophysiology to clinical management, Nat Rev Endocrinol,
doi:10.1038/s41574-020-00435-4Montefusco, Nasr, 'addio, Loretelli, Rossi et al., Acute and long-term disruption of glycometabolic control after SARS-CoV-2 infection, Nat Metab,
doi:10.1038/s42255-021-00407-6Prete, Favoino, Catacchio, Racanelli, Perosa, SARS-CoV-2 inflammatory syndrome. Clinical features and rationale for immunological treatment, Int J Mol Sci,
doi:10.3390/ijms21093377Ren, Luo, Yu, Song, Liang et al., A randomized, open-label, controlled clinical trial of azvudine tablets in the treatment of mild and common COVID-19, a pilot study, Adv Sci,
doi:10.1002/advs.202001435Seyit, Avci, Nar, Senol, Yilmaz et al., Neutrophil to lymphocyte ratio, lymphocyte to monocyte ratio and platelet to lymphocyte ratio to predict the severity of COVID-19, Am J Emerg Med,
doi:10.1016/j.ajem.2020.11.058Shi, Zhang, Jiang, Zhang, Hu et al., Clinical characteristics and risk factors for mortality of COVID-19 patients with diabetes in wuhan, China: A two-center, retrospective study, Diabetes Care,
doi:10.2337/dc20-0598Singh, Gillies, Singh, Singh, Chudasama et al., Prevalence of co-morbidities and their association with mortality in patients with COVID-19: A systematic review and meta-analysis, Diabetes Obes Metab,
doi:10.1111/dom.v22.10Sun, Dian, Shen, Zeng, Chen, Oral azvudine for hospitalised patients with COVID-19 and pre-existing conditions: A retrospective cohort study, EClinicalMedicine,
doi:10.1016/j.eclinm.2023.101981Who, WHO COVID-19 dashboard
Who, WHO recommends highly successful COVID-19 therapy and calls for wide geographical distribution and transparency from originator
Who, WHO updates its treatment guidelines to include molnupiravir
Wu, He, Huang, Guo, Li et al., Azvudine for the treatment of COVID-19 in pre-existing cardiovascular diseases: A single-center, real-world experience, Adv Sci,
doi:10.1002/advs.202306050Wu, Mcgoogan, Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: Summary of a report of 72 314 cases from the Chinese center for disease control and prevention, JAMA,
doi:10.1001/jama.2020.2648Yu, Li, Sun, Wang, 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, Li, Wang, Liu, Lu et al., Azvudine is a thymushoming anti-SARS-CoV-2 drug effective in treating COVID-19 patients, Signal Transduct Target Ther,
doi:10.1038/s41392-021-00835-6Zhu, Feng, Jiang, Mi, Yang et al., Correlation between white blood cell count at admission and mortality in COVID-19 patients: A retrospective study, BMC Infect Dis,
doi:10.1186/s12879-021-06277-3Zhu, She, Cheng, Qin, Zhang et al., 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.2020.04.021Zong, Zhou, Li, Jiang, Liu et al., Azvudine reduces the in-hospital mortality of COVID-19 patients: A retrospective cohort study, Acta Pharm Sin B,
doi:10.1016/j.apsb.2023.07.007
