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

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

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.

Keywords: effectiveness; pharmacoepidemiology; real‐world evidence; type 2 diabetes.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents* / therapeutic use
  • COVID-19 / complications
  • COVID-19 / epidemiology
  • COVID-19 / mortality
  • COVID-19 Drug Treatment*
  • Cytidine* / analogs & derivatives
  • Cytidine* / therapeutic use
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Drug Therapy, Combination
  • Female
  • Hong Kong / epidemiology
  • Hospitalization* / statistics & numerical data
  • Humans
  • Hydroxylamines / therapeutic use
  • Indoles / therapeutic use
  • Lactams
  • Leucine / analogs & derivatives
  • Leucine / therapeutic use
  • Male
  • Middle Aged
  • Nitriles
  • Proline
  • Ritonavir* / therapeutic use
  • SARS-CoV-2
  • Treatment Outcome

Substances

  • Ritonavir
  • Cytidine
  • molnupiravir
  • Antiviral Agents
  • nirmatrelvir
  • Leucine
  • Hydroxylamines
  • Indoles
  • Lactams
  • Nitriles
  • Proline