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This analysis evaluates the effectiveness of Azvudine versus Nirmatrelvir/Ritonavir in COVID-19 patients with diabetes.

March 13, 2026Open Access

A real-world retrospective analysis comparing the effectiveness of Azvudine and Nirmatrelvir/Ritonavir in COVID-19 patients with diabetes

Key Points

This analysis evaluates the effectiveness of Azvudine versus Nirmatrelvir/Ritonavir in COVID-19 patients with diabetes.
Retrospective study of 13,763 hospitalized COVID-19 patients with diabetes.
Patients were treated with either Azvudine (288) or Nirmatrelvir/Ritonavir (112).
Propensity-score matching used for direct comparison of treatment effects.
Composite outcome included all-cause mortality, ICU admission, and invasive mechanical ventilation.
41 deaths recorded during hospitalization or post-discharge follow-up.
No significant differences found in composite outcomes between both treatment groups.
Nirmatrelvir/Ritonavir showed a non-significant trend toward lower all-cause mortality (HR = 0.502).
Patients with severe diabetes had an associated hazard ratio of 0.37 for Nirmatrelvir/Ritonavir.
Patients treated with Nirmatrelvir/Ritonavir had lower incidence of myocardial injury.

Abstract

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. In this retrospective study, data from 13,763 hospitalized COVID-19 patients with comorbid diabetes mellitus between December 5, 2022, and January 31, 2023, were analyzed. 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 were collected retrospectively 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. 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 a non-significant trend toward lower all-cause mortality (aHR = 0.502, 95% CI: 0.133–1.180) 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 was associated with a hazard ratio of 0.37 (95% CI: 0.11–1.00), corresponding to a 63% point-estimate reduction in mortality risk. In severe diabetes patients (HR = 0.37, 95% CI: 0.11–1.00), although this result did not reach statistical significance. Regarding outcome measures, patients with diabetes and COVID-19 infection treated with Nirmatrelvir/Ritonavir demonstrated a lower incidence of myocardial injury and a non-significant trend toward reduced mortality, but no significant difference in the composite endpoint. compared to those treated with Azvudine.

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