A study published in JAMA Internal Medicine, a secondary analysis of the DANFLU-2 randomized clinical trial in Denmark, indicates that high-dose influenza vaccines are associated with lower rates of specific influenza-related hospitalizations compared to standard-dose vaccines in older adults, including those with and without diabetes.
Influenza, an acute respiratory infection, affects approximately 1 billion people globally each year, with 3 to 5 million severe cases and 290,000 to 650,000 related deaths. While typically mild, the infection poses higher risks of severe respiratory and cardiovascular complications for children under five, older adults, and individuals with comorbidities like diabetes. Standard-dose inactivated influenza vaccines have shown suboptimal protection, especially in high-risk groups.
The high-dose inactivated influenza vaccine, which contains four times the antigen levels of standard vaccines, was developed to address the significant impact of influenza. It is currently the preferred vaccine for U.S. adults aged 65 and older. This study aimed to compare the protective efficacy of high-dose and standard-dose influenza vaccines in older adults, including those with diabetes, as a prespecified secondary analysis of the DANFLU-2 randomized clinical trial in Denmark.
The study involved 332,438 older adults, of whom 43,881 had diabetes. Participants were randomly assigned to either a high-dose or standard-dose vaccination group. They were monitored from 14 days post-vaccination until May 31 of the subsequent year. Researchers evaluated the vaccines' efficacy on predefined cardiorespiratory, cardiovascular, and influenza-related hospitalization outcomes in both diabetic and non-diabetic participants.
The analysis indicated that the high-dose influenza vaccine was associated with lower hospitalization rates for several outcomes in older adults, particularly influenza-related hospitalizations. This effect was consistent regardless of diabetes status. No significant differences were observed for overall respiratory disease or myocardial infarction hospitalizations. Among diabetes subgroups, longer diabetes duration was associated with a lower incidence of cardiorespiratory hospitalizations with high-dose vaccination, an effect not seen in those with shorter duration diabetes.
The study suggests a potential additional benefit of high-dose influenza vaccine in reducing hospitalizations for certain cardiorespiratory and cardiovascular outcomes, including influenza, in older adults, irrespective of diabetes status. The authors note that these secondary and subgroup analyses are exploratory, considering the DANFLU-2 trial's neutral primary endpoint regarding hospitalization for influenza or pneumonia. Public health authorities recommend annual influenza vaccination, especially for individuals with chronic conditions like diabetes, due to their increased vulnerability to complications. The study observed a higher risk of cardiorespiratory and cardiovascular complications in participants with diabetes, underscoring the need for optimized preventive strategies. The absolute benefit of high-dose vaccination appeared greater in individuals with diabetes. While a consistent trend towards reduced hospitalizations for cardiorespiratory disease, cardiovascular disease, and heart failure was reported with high-dose vaccination, some diabetes-specific estimates lacked statistical significance. No overall reduction in cardiovascular death was observed.
The study also explored the influence of diabetes characteristics such as duration and glycemic control on vaccine associations, suggesting that high-dose vaccination benefits might be more pronounced in individuals with advanced diabetes. These subgroup findings are considered hypothesis-generating. The authors theorize that individuals with greater disease burden might have a more suboptimal immune response to standard-dose vaccines and higher susceptibility to influenza complications. The study concludes that high-dose influenza vaccination may provide enhanced benefits against certain severe outcomes in vulnerable populations through a single annual intervention. It is noted that the DANFLU-2 trial data were not powered for subgroup analyses, making these findings exploratory. Limitations included lack of access to follow-up laboratory data (e.g., glycated hemoglobin levels) and Danish prescription registries, which prevented the inclusion of medication data in baseline or endpoint definitions and limited the ability to determine treatment patterns or group balance regarding agents like GLP-1 receptor agonists and SGLT-2 inhibitors.