比较莫努匹韦和奈玛特韦-利托那韦在非住院和住院 COVID-19 合并 2 型糖尿病患者中的疗效：一项目标试验模拟研究。

Comparing the effectiveness of molnupiravir and nirmatrelvir-ritonavir in non-hospitalized and hospitalized COVID-19 patients with type 2 diabetes: A target trial emulation study.

机构信息

Centre for Safe Medication Practice and research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.

Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, China.

出版信息

Diabetes Obes Metab. 2024 Oct;26(10):4653-4664. doi: 10.1111/dom.15830. Epub 2024 Aug 7.

DOI:10.1111/dom.15830

PMID:39109461

Abstract

AIMS

To compare the effectiveness of molnupiravir and nirmatrelvir-ritonavir for non-hospitalized and hospitalized COVID-19 patients with type 2 diabetes (T2DM).

MATERIALS AND METHODS

Territory-wide electronic health records in Hong Kong were used to perform target trial emulation using a sequential trial approach. Patients (1) aged ≥18 years, (2) with T2DM, (3) with COVID-19 infection, and (4) who received molnupiravir or nirmatrelvir-ritonavir within 5 days of infection between 16 March 2022 and 31 December 2022 in non-hospital and hospital settings were included. Molnupiravir and nirmatrelvir-ritonavir initiators were matched using one-to-one propensity-score matching and followed for 28 days. Risk of outcomes was compared between groups by Cox regression adjusted for baseline characteristics. Subgroup analyses were performed on age (<70 years, ≥70 years), sex, Charlson comorbidity index (<4, ≥4), and number of COVID-19 vaccine doses (<2 doses, ≥2 doses).

RESULTS

Totals of 17 974 non-hospitalized (8987 in each group) and 3678 hospitalized (1839 in each group) patients were identified. Non-hospitalized nirmatrelvir-ritonavir initiators had lower risk of all-cause mortality (absolute risk reduction [ARR] at 28 days 0.80%, 95% confidence interval [CI] 0.56-1.04; hazard ratio [HR] 0.47, 95% CI 0.30-0.73) and hospitalization (ARR at 28 days 4.01%, 95% CI 3.19-4.83; HR 0.73, 95% CI 0.66-0.82) as compared with molnupiravir initiators. Hospitalized nirmatrelvir-ritonavir initiators had reduced risk of all-cause mortality (ARR at 28 days 2.94%, 95% CI 1.65-4.23; HR 0.56, 95% CI 0.40-0.80) as compared with molnupiravir initiators. Consistent findings were found across all subgroups.

CONCLUSIONS

The use of nirmatrelvir-ritonavir may be preferred to molnupiravir for COVID-19 patients with T2DM and without contraindication to either treatment.

摘要

目的

比较莫努匹韦和奈玛特韦/利托那韦在非住院和住院 COVID-19 合并 2 型糖尿病（T2DM）患者中的疗效。

材料和方法

利用香港全地域电子健康记录，采用序贯试验方法进行目标试验模拟。符合以下条件的患者纳入研究：（1）年龄≥18 岁；（2）患有 T2DM；（3）COVID-19 感染；（4）在 2022 年 3 月 16 日至 12 月 31 日期间感染后 5 天内接受莫努匹韦或奈玛特韦/利托那韦治疗的非住院和住院患者。采用 1:1 倾向评分匹配对莫努匹韦和奈玛特韦/利托那韦的起始治疗者进行匹配，并随访 28 天。通过 Cox 回归调整基线特征比较两组之间的结局风险。对年龄（<70 岁、≥70 岁）、性别、Charlson 合并症指数（<4、≥4）和 COVID-19 疫苗接种剂数（<2 剂、≥2 剂）进行亚组分析。

结果

共纳入 17974 例非住院（每组 8987 例）和 3678 例住院（每组 1839 例）患者。与莫努匹韦相比，非住院奈玛特韦/利托那韦起始治疗者的全因死亡率（28 天绝对风险降低率[ARR]为 0.80%，95%置信区间[CI]为 0.56-1.04；风险比[HR]为 0.47，95%CI 为 0.30-0.73）和住院率（28 天 ARR 为 4.01%，95%CI 为 3.19-4.83；HR 为 0.73，95%CI 为 0.66-0.82）较低。与莫努匹韦相比，住院奈玛特韦/利托那韦起始治疗者的全因死亡率风险降低（28 天 ARR 为 2.94%，95%CI 为 1.65-4.23；HR 为 0.56，95%CI 为 0.40-0.80）。所有亚组均观察到一致的结果。