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

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.