Effectiveness of Molnupiravir and Nirmatrelvir-Ritonavir in COVID-19 Patients with Type-2 Diabetes

Abstract

<p>Background:<br>Emerging evidence suggested the significantly increased risk of all-cause mortality in COVID-19<br>patients with type-2 diabetes. However, direct comparison on the effectiveness of molnupiravir and<br>nirmatrelvir-ritonavir among COVID-19 patients with type-2 diabetes remains scarce.<br>Aims:<br>To compare the effectiveness of molnupiravir and nirmatrelvir-ritonavir for COVID-19 patients with<br>type-2 diabetes in non-hospitalised and hospitalised settings.<br>Methods:<br>Target trial emulation was conducted using territory-wide electronic health databases in Hong Kong.<br>A sequential trial approach was adopted. Adults with type-2 diabetes who had a COVID-19 infection<br>and initiated either molnupiravir or nirmatrelvir-ritonavir within five days of infection between 16<br>March 2022 and 31 December 2022 were included. One-to-one propensity score matching was<br>applied between treatment groups. Each subject was followed from index date (date of molnupiravir<br>or nirmatrelvir-ritonavir initiation) until the earliest occurrence of all-cause mortality, 28 days from<br>index date or the end of data availability (31 January 2023). Risk of all-cause mortality between<br>treatment groups in non-hospitalised and hospitalised settings was compared by Cox regression<br>adjusted with baseline characteristics. Subgroup analyses were performed with age (<70, ≥70 years),<br>sex, Charlson comorbidity index (<4, ≥4), and number of COVID-19 vaccine doses (0-1, ≥2 doses).<br>Results:<br>17,974 non-hospitalised (8,987 per treatment group) and 3,678 hospitalised (1,839 per treatment<br>group) patients were identified. Nirmatrelvir-ritonavir users had lower risk of all-cause mortality as<br>compared with molnupiravir users in both non-hospitalised (absolute risk reduction [ARR] at 28 days Background:<br>Emerging evidence suggested the significantly increased risk of all-cause mortality in COVID-19<br>patients with type-2 diabetes. However, direct comparison on the effectiveness of molnupiravir and<br>nirmatrelvir-ritonavir among COVID-19 patients with type-2 diabetes remains scarce.<br>Aims:<br>To compare the effectiveness of molnupiravir and nirmatrelvir-ritonavir for COVID-19 patients with<br>type-2 diabetes in non-hospitalised and hospitalised settings.<br>Methods:<br>Target trial emulation was conducted using territory-wide electronic health databases in Hong Kong.<br>A sequential trial approach was adopted. Adults with type-2 diabetes who had a COVID-19 infection<br>and initiated either molnupiravir or nirmatrelvir-ritonavir within five days of infection between 16<br>March 2022 and 31 December 2022 were included. One-to-one propensity score matching was<br>applied between treatment groups. Each subject was followed from index date (date of molnupiravir<br>or nirmatrelvir-ritonavir initiation) until the earliest occurrence of all-cause mortality, 28 days from<br>index date or the end of data availability (31 January 2023). Risk of all-cause mortality between<br>treatment groups in non-hospitalised and hospitalised settings was compared by Cox regression<br>adjusted with baseline characteristics. Subgroup analyses were performed with age (<70, ≥70 years),<br>sex, Charlson comorbidity index (<4, ≥4), and number of COVID-19 vaccine doses (0-1, ≥2 doses).<br>Results:<br>17,974 non-hospitalised (8,987 per treatment group) and 3,678 hospitalised (1,839 per treatment<br>group) patients were identified. Nirmatrelvir-ritonavir users had lower risk of all-cause mortality as<br>compared with molnupiravir users in both non-hospitalised (absolute risk reduction [ARR] at 28 days<br></p>