Effects of high-dose versus standard-dose quadrivalent influenza vaccine among patients with diabetes: a post-hoc analysis of the DANFLU-1 trial

Journal article

Aim: High-dose quadrivalent influenza vaccine (QIV-HD) has been shown to be more effective than standard-dose (QIV-SD) in reducing influenza infection, but whether diabetes status affects relative vaccine effectiveness (rVE) is unknown. We aimed to assess rVE on change in glycated haemoglobin [HbA1c (∆HbA1c)], incident diabetes, total all-cause hospitalizations (first + recurrent), and a composite of all-cause mortality and hospitalization for pneumonia or influenza.

Methods: DANFLU-1 was a pragmatic, open-label trial randomizing adults (65-79 years) 1:1 to QIV-HD or QIV-SD during the 2021/22 influenza season. Cox proportional hazards regression was used to estimate rVE against incident diabetes and the composite endpoint, negative binomial regression to estimate rVE against all-cause hospitalizations, and ANCOVA when assessing rVE against ∆HbA1c.

Results: Of the 12 477 participants, 1162 (9.3%) had diabetes at baseline. QIV-HD, compared with QIV-SD, was associated with a reduction in the rate of all-cause hospitalizations irrespective of diabetes [overall: 647 vs. 742 events, incidence rate ratio (IRR): 0.87, 95% CI (0.76-0.99); diabetes: 93 vs. 118 events, IRR: 0.80, 95% CI (0.55-1.15); without diabetes: 554 vs. 624 events, IRR: 0.88, 95% CI (0.76-1.01), p_interaction = 0.62]. Among those with diabetes, QIV-HD was associated with a lower risk of the composite outcome [2 vs. 11 events, HR: 0.18, 95% CI (0.04-0.83)] but had no effect on ∆HbA1c; QIV-HD adjusted mean difference: ∆ + 0.2 mmol/mol, 95% CI (−0.9 to 1.2). QIV-HD did not affect the risk of incident diabetes [HR 1.18, 95% CI (0.94-1.47)].

Conclusions: In this post-hoc analysis, QIV-HD versus QIV-SD was associated with an increased rVE against the composite of all-cause death and hospitalization for pneumonia/influenza, and the all-cause hospitalization rate irrespective of diabetes status.

Authors: Lassen, MCH; Johansen, ND; Modin, D; Nealon, J; Samson, S

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Wiley
• Journal: Diabetes, Obesity and Metabolism
• Volume: 26
• Issue: 5
• Pages: 1821-1829
• Publication date: 2024-04-08
• Acceptance date: 2024-01-31
• DOI: 10.1111/dom.15498
• EISSN: 1463-1326
• ISSN: 1462-8902
• Pmid: 38586966
• Language: English
• Keywords: diabetes; pragmatic; pneumonia; influenza vaccines; diabetes mellitus; human influenza; hospitalization; influenza; randomized controlled trial; aged; vaccine; pragmatic clinical trials as topic; registry