Effectiveness of Azvudine Compared to Nirmatrelvir/Ritonavir in COVID-19 Patients with Diabetes: A Real-World Retrospective Analysis

Backgrounds: Azvudine and Nirmatrelvir/ritonavir have been approved for the treatment of mild to moderate COVID-19 in adults at high risk for progression to severe disease. Diabetes is a high-risk complication of COVID-19. Currently, the effectiveness of Azvudine and Nirmatrelvir/ritonavir in patients with both diabetes and COVID-19 remains unclear. This study aims to compare the effectiveness of these two drugs in patients with diabetes and COVID-19. Methods: In this retrospective study. Our team enrolled 13763 hospitalized patients with COVID-19 infection presenting with comorbid diabetes mellitus between December 5, 2022, and January 31, 2023. These patients were from six different hospitals in the GuangXi Zhuang Autonomous Region, including 288 patients treated with Azvudine and 112 patients treated with Nirmatrelvir/Ritonavir. The primary outcome comprised a composite endpoint of disease progression, characterized by all-cause mortality, intensive care unit (ICU) admission, or need for invasive mechanical ventilation. Data for all participants were retrospectively collected through electronic medical record review supplemented by telephone follow-up. We used propensity-score matching (PSM) to allow for a more direct comparison of the effectiveness between the two antiviral treatment groups. Findings: Among 400 enrolled patients, 41 deaths occurred during hospitalization or post-discharge follow-up (Azvudine group: n = 29; Nirmatrelvir/ritonavir group: n = 12). After propensity score matching (PSM), 17 deaths were recorded across both cohorts. Statistical analysis demonstrated no significant between-group differences in composite outcomes (including invasive mechanical ventilation and ICU admission). However, Nirmatrelvir/ritonavir showed superior efficacy for all-cause mortality reduction versus Azvudine (Crude HR = 0.502; Adjusted HR [aHR] = 0.502, 95% CI: 0.133-1.180). Glucocorticoid use during therapy was associated with reduced mortality risk, while concomitant anticoagulant therapy increased composite outcome risk. Findings indicated a progressive elevation in mortality risk with advancing diabetes severity grade. Notably, Nirmatrelvir/ritonavir reduced mortality by 63% in severe diabetes patients (HR = 0.37, 95% CI: 0.11-1.00). Interpretation Regarding outcome measures, patients with diabetes and COVID-19 infection treated with Nirmatrelvir/ritonavir demonstrated superior outcomes compared to those treated with Azvudine.