High-dose influenza vaccine protects older adults with diabetes against severe outcomes
- 23-01-2026
- Diabetes
- Editor's Choice
- News
medwireNews: The high-dose inactivated influenza vaccine (HD-IIV) offers older adults greater protection against hospitalizations for cardiorespiratory-, cardiovascular-, and influenza-related causes than the standard-dose (SD)-IIV, regardless of their diabetes status, research shows.
“These findings, while exploratory, underscore the importance of influenza vaccination and suggest potential benefit of HD-IIV compared with SD-IIV in individuals with diabetes,” say Tor Biering-Sørensen (Copenhagen University Hospital–Herlev and Gentofte, Denmark) and co-investigators.
They explain that the HD-IIV, which contains a four-fold higher antigen content than the SD-IIV, has already shown superior efficacy against influenza infection among older adults, but the relative vaccine effectiveness (rVE) of the HD-IIV versus the SD-IIV for the prevention of severe clinical outcomes in people with diabetes is unclear.
To address this, Biering-Sørensen and team carried out a prespecified secondary analysis of the DANFLU-2 trial, in which 332,438 individuals aged 65 years and older (mean age 74 years, 49% women) were randomly assigned to receive HD-IIV or SD-IIV. Of these, 13.2% had diabetes.
The researchers report in the Annals of Internal Medicine that, overall, the rates of hospitalization for any cardiorespiratory disease, any cardiovascular disease, heart failure, influenza, and laboratory-confirmed influenza were lower with the HD-IIV than with the SD-IIV.
Among those tested for influenza, the rates of infection were similar between the participants with (n=170) and without (n=840) diabetes, at 8.9% and 9.8%, respectively, yet the risks for severe outcomes were generally higher in the group with diabetes, with relative risks ranging from 1.34 for stroke hospitalizations to 3.26 for heart failure hospitalizations.
Despite having higher risks for severe outcomes, the HD-IIV remained similarly more effective than the SD-IIV in people with diabetes versus those without, when rVE was calculated as 1 minus the relative risk for the end point and presented as a percentage.
Specifically, the rVE of the HD-IIV versus the SD-IIV for the prevention of cardiorespiratory hospitalization was 7.4% among people with diabetes and 5.3% among those without diabetes, a nonsignificant difference.
Corresponding rVEs were a statistically comparable 12.0% and 6.0% for cardiovascular hospitalization, 41.6% and 44.3% for influenza-related hospitalization, 19.2% and 19.7% for hospitalization for heart failure, and 1.7% and 4.3% for hospitalization for any respiratory disease.
Biering-Sørensen et al comment: “Among individuals with diabetes, the consistent benefits of HD-IIV vs SD-IIV against hospitalizations for cardiorespiratory disease, cardiovascular disease, and heart failure support the case for using influenza vaccination not only to prevent influenza infection but also to reduce related cardiovascular events.”
The researchers also showed that, across the outcomes favoring HD-IIV, the numbers needed to vaccinate to prevent one case of each adverse outcome were lower among individuals with versus without diabetes, “reflecting their higher baseline risk and suggesting greater absolute benefit [of vaccination] for these end points in this population,” they remark.
HD-IIV benefits may vary by diabetes characteristics
Finally, the team carried out subgroup analyses by diabetes duration, glycated hemoglobin (HbA1c) level, and the presence of diabetes-related complications. They found that HD-IIV was associated with a reduced risk for hospitalization for cardiorespiratory reasons, major adverse cardiovascular events (MACE), heart failure, and stroke relative to SD-IIV in participants with a diabetes duration longer than 5 years, but not in those with a shorter diabetes duration.
Similarly, the benefits of HD-IIV over SD-IIV for reducing the risk for hospitalization of heart failure or MACE relative to SD-IIV were apparent in people with a diabetes-related complication but not in those without such complications.
For HbA1c, the benefit of HD-IIV over SD-IIV against stroke was only significant in people with an HbA1c above 6.5% (48 mmol/mol).
Biering-Sørensen and co-authors conclude: “Although exploratory and requiring confirmation in future research, these findings could imply that for certain end points, the protective benefits of HD-IIV compared with SD-IIV may be more prominent in individuals with more advanced diabetes.”
They suggest: “This could reflect a potentially more pronounced suboptimal immune response to SD-IIV among individuals with greater disease burden, in addition to the increased susceptibility to influenza-related complications associated with longer disease duration and comorbidity burden.”
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