High-dose flu vaccine reduces hospitalizations
In adults 65 years or older, a high-dose influenza vaccine modestly reduced several hospitalization outcomes compared with a standard-dose vaccine, with similar benefit in people with and without diabetes.
*Pragmatic open-label randomized clinical trial (secondary analysis); Level 1b.

Citation

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 Internal Medicine. 2026;186(3):311-320. doi:10.1001/jamainternmed.2025.7286

Background

Older adults, especially those with diabetes, have higher risks of severe illness from influenza. High-dose influenza vaccines prevent influenza infection better than standard-dose vaccines, but evidence for severe heart and lung outcomes in diabetes has been limited.

Patients

Adults 65 years or older in Denmark (2022/2023 to 2024/2025 influenza seasons); no formal exclusion criteria. Total: 332,438 participants; 43,881 had diabetes.

Intervention

High-dose inactivated influenza vaccine (single seasonal injection).

Control

Standard-dose inactivated influenza vaccine.

Outcome

Hospitalizations for combined heart/lung disease, heart disease, influenza, lab-confirmed influenza, and heart failure; comparison by diabetes status and diabetes subgroups.

Follow-up Period

From 14 days after vaccination to May 31 each season.

Results

Outcome High-dose vs standard-dose (relative reduction) NNT
Hospitalization for any heart/lung disease 5.7% (1.4% to 9.9%) 1000
Hospitalization for any heart disease 7.2% (1.5% to 12.5%) 1000
Hospitalization for influenza 43.6% (27.6% to 56.2%) 2132
Hospitalization for lab-confirmed influenza 35.9% (22.3% to 47.2%) 1678
Hospitalization for heart failure 19.5% (3.3% to 33.1%) 3205
Effects were generally similar in participants with and without diabetes. In exploratory subgroup analyses, people with diabetes for more than 5 years appeared to benefit more for some outcomes.
Analysis was intention-to-treat.

Limitations

Secondary and subgroup analyses were not the main trial focus and involved multiple comparisons without adjustment, so some findings may be due to chance. The trial was open-label and relied on registry records. Although relative reductions were significant for several outcomes, the absolute benefits were small (high NNTs), which may limit day-to-day clinical impact.

Funding

Sanofi; additional support from Danish cardiovascular research foundations.

Clinical Application

For adults 65+ (including diabetes), consider high-dose influenza vaccine when available; absolute benefit is modest, but may be larger in longer-standing diabetes.