Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
JAMA Netw Open. 2023 May 1;6(5):e2314393. doi: 10.1001/jamanetworkopen.2023.14393.
Diabetes and COVID-19 are both global pandemics, and type 2 diabetes is a common comorbidity in patients with acute COVID-19 and is proven to be a key determinant of COVID-19 prognosis. Molnupiravir and nirmatrelvir-ritonavir are oral antiviral medications recently approved for nonhospitalized patients with mild to moderate COVID-19, following demonstration of their efficacies in reducing adverse outcomes of the disease; it is crucial to clarify whether both oral antiviral medications are efficacious in a population consisting exclusively of patients with type 2 diabetes.
To evaluate the effectiveness of molnupiravir and nirmatrelvir-ritonavir in a contemporary population-based cohort comprising exclusively nonhospitalized patients with type 2 diabetes and SARS-CoV-2 infection.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was performed using population-based electronic medical record data for patients in Hong Kong with type 2 diabetes and confirmed SARS-CoV-2 infection between February 26 and October 23, 2022. Each patient was followed up until death, outcome event, crossover of oral antiviral treatment, or end of the observational period (October 30, 2022), whichever came first. Outpatient oral antiviral users were divided into molnupiravir and nirmatrelvir-ritonavir treatment groups, respectively, and nontreated control participants were matched through 1:1 propensity score matching. Data analysis was performed on March 22, 2023.
Molnupiravir (800 mg twice daily for 5 days) or nirmatrelvir-ritonavir (300 mg nirmatrelvir and 100 mg ritonavir twice daily for 5 days, or 150 mg nirmatrelvir and 100 mg ritonavir for patients with an estimated glomerular filtration rate of 30-59 mL/min per 1.73 m2).
The primary outcome was a composite of all-cause mortality and/or hospitalization. The secondary outcome was in-hospital disease progression. Hazard ratios (HRs) were estimated with Cox regression.
This study identified 22 098 patients with type 2 diabetes and COVID-19. A total of 3390 patients received molnupiravir and 2877 received nirmatrelvir-ritonavir in the community setting. After application of exclusion criteria followed by 1:1 propensity score matching, this study comprised 2 groups. One group included 921 molnupiravir users (487 men [52.9%]), with a mean (SD) age of 76.7 (10.8) years, and 921 control participants (482 men [52.3%]), with a mean (SD) age of 76.6 (11.7) years. The other group included 793 nirmatrelvir-ritonavir users (401 men [50.6%]), with a mean (SD) age of 71.7 (11.5) years, and 793 control participants (395 men [49.8%]), with a mean (SD) age of 71.9 (11.6) years. At a median follow-up of 102 days (IQR, 56-225 days), molnupiravir use was associated with a lower risk of all-cause mortality and/or hospitalization (HR, 0.71 [95% CI, 0.64-0.79]; P < .001) and in-hospital disease progression (HR, 0.49 [95% CI, 0.35-0.69]; P < .001) compared with nonuse. At a median follow-up of 85 days (IQR, 56-216 days), nirmatrelvir-ritonavir use was associated with a lower risk of all-cause mortality and/or hospitalization (HR, 0.71 [95% CI, 0.63-0.80]; P < .001) and a nonsignificantly lower risk of in-hospital disease progression (HR, 0.92 [95% CI, 0.59-1.44]; P = .73) compared with nonuse.
These findings suggest that both molnupiravir and nirmatrelvir-ritonavir oral antiviral medications were associated with a lower risk of all-cause mortality and hospitalization among patients with COVID-19 and type 2 diabetes. Further studies in specific populations, such as individuals in residential care homes and individuals with chronic kidney disease, are suggested.
糖尿病和 COVID-19 都是全球性的大流行病，2 型糖尿病是急性 COVID-19 患者的常见合并症，并已被证明是 COVID-19 预后的关键决定因素。莫那比拉韦和奈玛特韦-利托那韦是最近批准用于轻度至中度 COVID-19 的非住院患者的口服抗病毒药物，在证明其降低疾病不良结局的疗效后；澄清这两种口服抗病毒药物在仅由 2 型糖尿病患者组成的人群中是否有效至关重要。
评估莫那比拉韦和奈玛特韦-利托那韦在一个基于人群的当代队列中的有效性，该队列仅包括患有 2 型糖尿病和 SARS-CoV-2 感染的非住院患者。
设计、地点和参与者：这项回顾性队列研究使用了香港的基于人群的电子病历数据，这些数据来自于 2022 年 2 月 26 日至 10 月 23 日期间确诊为 SARS-CoV-2 感染的 2 型糖尿病患者。每位患者的随访时间直到死亡、结局事件、口服抗病毒治疗交叉或观察期结束（2022 年 10 月 30 日），以先发生者为准。门诊口服抗病毒药物使用者分别分为莫那比拉韦和奈玛特韦-利托那韦治疗组，未接受治疗的对照组通过 1:1 倾向评分匹配。数据分析于 2023 年 3 月 22 日进行。
莫那比拉韦（800 mg，每日 2 次，连用 5 天）或奈玛特韦-利托那韦（300 mg 奈玛特韦和 100 mg 利托那韦，每日 2 次，连用 5 天，或 150 mg 奈玛特韦和 100 mg 利托那韦用于估计肾小球滤过率为 30-59 mL/min/1.73 m2 的患者）。
主要结局是全因死亡率和/或住院率的复合结局。次要结局是住院期间疾病进展。使用 Cox 回归估计风险比（HR）。
这项研究纳入了 22098 名患有 2 型糖尿病和 COVID-19 的患者。共有 3390 名患者在社区环境中接受了莫那比拉韦治疗，2877 名患者接受了奈玛特韦-利托那韦治疗。在应用排除标准并进行 1:1 倾向评分匹配后，本研究包括 2 组。一组包括 921 名莫那比拉韦使用者（487 名男性[52.9%]），平均（SD）年龄为 76.7（10.8）岁，921 名对照组参与者（482 名男性[52.3%]），平均（SD）年龄为 76.6（11.7）岁。另一组包括 793 名奈玛特韦-利托那韦使用者（401 名男性[50.6%]），平均（SD）年龄为 71.7（11.5）岁，793 名对照组参与者（395 名男性[49.8%]），平均（SD）年龄为 71.9（11.6）岁。在中位随访 102 天（IQR，56-225 天）期间，与未使用者相比，莫那比拉韦使用者的全因死亡率和/或住院率（HR，0.71 [95%CI，0.64-0.79]；P <.001）和住院期间疾病进展（HR，0.49 [95%CI，0.35-0.69]；P <.001）风险较低。在中位随访 85 天（IQR，56-216 天）期间，与未使用者相比，奈玛特韦-利托那韦使用者的全因死亡率和/或住院率（HR，0.71 [95%CI，0.63-0.80]；P <.001）和住院期间疾病进展（HR，0.92 [95%CI，0.59-1.44]；P =.73）风险较低。
这些发现表明，莫那比拉韦和奈玛特韦-利托那韦这两种口服抗病毒药物均与 COVID-19 和 2 型糖尿病患者的全因死亡率和住院风险降低相关。建议在特定人群（如居住在养老院的个体和慢性肾脏病患者）中进行进一步研究。
