European Safety Analysis of mRNA and Viral Vector COVID-19 Vaccines on Glucose Metabolism Events

ABSTRACT

Introduction: COVID-19 is a complex disease with several clinical phases of progression, affecting many organs apart from the respiratory tract that has shown a worst prognosis in both patients with type 1 and type 2 diabetes mellitus [1]. Based on these considerations, the vaccination for COVID-19 is a priority for this subpopulation [2]. However, few data have been published on the effects of impaired glucose metabolism induced by COVID-19 vaccines. Objective(s) We decided to perform a study to describe Individual Case Safety Reports (ICSRs) of impaired glucose metabolism events reported in the European database (Eudravigilance, EV). Method(s) ICSRs were retrieved for the period from January 1st, 2021 to December 11th, 2021. An ICSR related to events of impaired glucose metabolism was identified by using selected preferred terms (PTs) from Standardized MedDRA Queries ''Hyperglycaemia/new onset diabetes mellitus'' and ''Hypoglycaemia''. Impaired glucose metabolism events were described and analyzed based on the Diabetologists' classification into nine groups ''diabetes in pregnancy'', ''acute complications of diabetes'', ''pre-diabetes'', ''type 1 diabetes mellitus'', ''type 2 diabetes mellitus'', ''high glucose levels'', ''diabetes mellitus inadequate control'', ''diabetes melli-tus not specified'', and ''hypoglycaemia''. The reporting odds ratios were computed to assess the reporting frequency for COVID-19 mRNA vaccines compared to COVID-19 viral vector-based vaccines. Result(s) During the study period, 3,917 ICSRs with a COVID-19 vaccine as suspected and at least an event of impaired glucose metabolism were retrieved from the EV, of which 2,027 (51.75%) referred to Pfizer-BioNTech vaccine, 586 (14.96%) to Moderna vaccine, 1,163 (29.70%) to Oxford-AstraZeneca vaccine, and 141 (3.59%) to Janssen vaccine. From 3,917 ICSRs, we observed 4,275 impaired glucose metabolism events (1.09 adverse events per ICSR). Most adverse events were classified as serious (2,694;63.02%), and the most reported events were related to ''high glucose levels'' (2,012;47.06%). The mRNA vaccines were associated with an increased reporting frequency of ''type 1 diabetes mellitus'' (ROR 1.86;95% CI 1.33-2.60), ''type 2 diabetes mellitus'' (ROR 1.58;95% CI 1.03-2.42), ''high glucose levels'' (ROR 1.16;95% CI 1.06-1.27), ''diabetes mellitus inadequate control'' (ROR 1.63;95% CI 1.25-2.11), and ''hypoglycemia'' (ROR 1.62;95% CI 1.41-1.86) compared to viral vector-based vaccines. The highest reporting rate per 100,000 was observed for Oxford-AstraZeneca vaccine (1.87;95% CI 1.77-1.97). Conclusion(s) In conclusion, mRNA COVID-19 vaccines were associated with an increased reporting frequency of alterations of glucose homeostasis compared to viral-vector COVID-19 vaccines. Clinicians should be aware of these events to better manage glycaemic perturbations. Larger nationwide studies are warranted to verify these findings.