High-Dose Influenza Vaccine Benefits Older Adults Regardless of Diabetes: JAMA
Trial results indicate that in adults 65 years and older, the high-dose inactivated influenza vaccine (HD-IIV) consistently reduced cardiorespiratory, cardiovascular, and influenza-related hospitalizations compared with the standard-dose vaccine (SD-IIV), irrespective of diabetes status. A new study was published in JAMA Internal Medicine conducted by Anne B. N. and fellow researchers.
Influenza infection is a major cause of morbidity and mortality in older adults, and individuals with diabetes have higher risks of serious complications on account of immune dysfunction and cardiovascular vulnerability. Though high-dose influenza vaccines have shown superior protection against laboratory-confirmed influenza in the past, evidence regarding their role in preventing grave downstream complications, particularly among people with diabetes, has been limited.
The main objective of this pre-defined secondary analysis was to assess the comparative vaccine effectiveness of high-dose inactivated influenza vaccine vs. standard-dose vaccine against severe respiratory and cardiovascular events. For this purpose, the analysis was performed on DANFLU-2, a pragmatic open-label individually randomized clinical trial performed among Danes during the 2022-2023 to 2024-2025 flu seasons. Adults aged 65 years or older without or with comorbidities could take part in the study. Information on vaccinations administered, hospitalizations, and outcomes was generated through the use of national Danish health registries. This was done between June and October 2025.
Key findings
A total of 332,438 participants were included in the analysis.
The mean (SD) age was 73.7 (5.8) years, and 161,538 participants (48.6%) were female. Among the participants, 43,881 (13.2%) had diabetes.
The participants were randomly assigned in a 1:1 ratio to receive high-dose inactivated influenza vaccine and standard-dose inactivated influenza vaccine.
In total, high-dose inactivated influenza vaccination was shown to decrease rates of cardiorespiratory, cardiovascular, and influenza hospitalizations compared with those receiving standard-dose inactivated vaccines.
Benefit was observed in participants with and without diabetes.
In cardiorespiratory hospitalization, the relative vaccine effectiveness was 7.4% (95% CI, -2.5 to 16.3) in subjects with diabetes and 5.3% (95% CI, 0.4 to 10) in those without, with no significant interaction (P = 0.69).
In cardiovascular hospitalization, the relative vaccine effectiveness was 12.0% (95% CI, -0.9 to 23.3) in subjects with diabetes and 6.0% (95% CI, -0.4 to 12) (P = 0.38).
Influenza hospitalization was reduced to a comparable extent in both, with relative vaccine effectiveness of 41.6% (95% CI, 5 to 64.7) in subjects with diabetes and 44.3% (95% CI, 25.3 to 58.7) (P = 0.87).
Those with diabetes for more than 5 years who were receiving high-dose vaccination had a relative vaccine effectiveness of 20.4% (95% CI, 5.3%-33.1%), whereas those with diabetes for 5 years or less did not show any benefit with high-dose vaccination, with a relative vaccine effectiveness of −0.4% (95% CI, −13.8% to 11.5%), with significant interaction (P = 0.03).
High-dose inactivated influenza vaccine was found to provide consistent protection against cardiorespiratory, cardiovascular, and flu-related hospitalizations in adults aged 65 years and older, with results agreeing regardless of the participant’s diabetes status. These outcomes can contribute to the preferred use of the vaccine among the elderly, thereby decreasing the severe outcomes of flu in the future.
Reference:
Nielsen AB, Johansen ND, Modin D, et al. High-Dose vs Standard-Dose Influenza Vaccine in Older Adults With Diabetes: A Secondary Analysis of the DANFLU-2 Randomized Clinical Trial. JAMA Intern Med. Published online January 12, 2026. doi:10.1001/jamainternmed.2025.7286
