tetano
Editor, Senior Moderator
JAMA Intern Med
. 2026 Jan 12.
doi: 10.1001/jamainternmed.2025.7286. Online ahead of print. High-Dose vs Standard-Dose Influenza Vaccine in Older Adults With Diabetes: A Secondary Analysis of the DANFLU-2 Randomized Clinical Trial
Anne Bjerg Nielsen[SUP] 1 2 [/SUP], Niklas Dyrby Johansen[SUP] 1 2 [/SUP], Daniel Modin[SUP] 1 2 [/SUP], Matthew M Loiacono[SUP] 3 4 [/SUP], Rebecca C Harris[SUP] 5 [/SUP], Marine Dufournet[SUP] 6 [/SUP], Carsten Schade Larsen[SUP] 7 8 [/SUP], Lykke Larsen[SUP] 9 [/SUP], Lothar Wiese[SUP] 10 [/SUP], Michael Dalager-Pedersen[SUP] 11 12 [/SUP], Brian L Claggett[SUP] 13 [/SUP], Kira Hyldekær Janstrup[SUP] 1 2 [/SUP], Katja Vu Bartholdy[SUP] 1 2 [/SUP], Katrine Feldballe Bernholm[SUP] 1 2 [/SUP], Julie Inge-Marie Helene Borchsenius[SUP] 1 2 [/SUP], Filip Søskov Davidovski[SUP] 1 2 [/SUP], Lise Witten Davodian[SUP] 1 2 [/SUP], Maria Dons[SUP] 1 2 [/SUP], Lisa Steen Duus[SUP] 1 2 [/SUP], Caroline Espersen[SUP] 1 2 [/SUP], Frederik Holme Fussing[SUP] 1 2 [/SUP], Anne Marie Reimer Jensen[SUP] 1 2 [/SUP], Nino Emanuel Landler[SUP] 1 2 [/SUP], Adam Cadovius Femerling Langhoff[SUP] 1 2 [/SUP], Mats Christian Højbjerg Lassen[SUP] 1 2 [/SUP], Camilla Ikast Ottosen[SUP] 1 2 [/SUP], Morten Sengeløv[SUP] 1 2 [/SUP], Kristoffer Grundtvig Skaarup[SUP] 1 2 [/SUP], Manan Pareek[SUP] 1 2 [/SUP], Dirk Müller-Wieland[SUP] 14 [/SUP], Scott D Solomon[SUP] 13 [/SUP], Martin J Landray[SUP] 15 [/SUP], Gunnar H Gislason[SUP] 1 16 17 [/SUP], Lars Køber[SUP] 16 18 [/SUP], Pradeesh Sivapalan[SUP] 16 19 [/SUP], Cyril Jean-Marie Martel[SUP] 20 [/SUP], Jens Ulrik Stæhr Jensen[SUP] 16 19 [/SUP], Tor Biering-Sørensen[SUP] 1 2 18 21 [/SUP]
Affiliations
Importance: Influenza infection poses a substantial risk of severe complications, particularly in older adults and high-risk populations, such as individuals with diabetes. The high-dose inactivated influenza vaccine (HD-IIV) has demonstrated superior efficacy against influenza infection compared with the standard-dose inactivated influenza vaccine (SD-IIV) among adults 65 years or older. However, there is limited evidence on its effectiveness in preventing severe respiratory and cardiovascular outcomes in individuals with diabetes.
Objective: To investigate the relative vaccine effectiveness (rVE) of HD-IIV vs SD-IIV against severe respiratory and cardiovascular outcomes according to diabetes status and across diabetes subgroups.
Design, setting, and participants: This was a prespecified secondary analysis of DANFLU-2, a pragmatic, open-label, individually randomized clinical trial conducted in Denmark during the 2022/2023 to 2024/2025 influenza seasons. Adults 65 years or older were eligible for inclusion regardless of comorbidities. Data were obtained from nationwide health registries and analyzed from June to October 2025.
Interventions: Participants were randomly allocated 1:1 to receive HD-IIV or SD-IIV.
Main outcomes and measures: Outcomes included respiratory and cardiovascular hospitalizations. The potential effect modification by diabetes status and across diabetes subgroups was tested.
Results: Among 332 438 participants (mean [SD] age, 73.7 [5.8] years; 161 538 female individuals [48.6%]), 43 881 (13.2%) had diabetes. Overall, HD-IIV compared with SD-IIV was associated with reduced cardiorespiratory hospitalization, cardiovascular hospitalization, and influenza hospitalization. Effect estimates were similar for participants with and without diabetes for cardiorespiratory hospitalization (diabetes: rVE, 7.4%; 95% CI, -2.5% to 16.3%; no diabetes: rVE, 5.3%; 95% CI, 0.4%-10.0%; interaction P = .69), cardiovascular hospitalization (diabetes: rVE, 12.0%; 95% CI, -0.9% to 23.3%; no diabetes: rVE, 6.0%; 95% CI, -0.4% to 12.0%; interaction P = .38), and influenza hospitalization (diabetes: rVE, 41.6%; 95% CI, 5.0%-64.7%, vs no diabetes: rVE, 44.3%; 95% CI, 25.3%-58.7%; interaction P = .87). Duration of diabetes appeared to modify the effect of HD-IIV vs SD-IIV for cardiorespiratory hospitalization, with suggested benefit of HD-IIV in participants with diabetes duration longer than 5 years (rVE, 20.4%; 95% CI, 5.3%-33.1%), but not in those with shorter duration (rVE, -0.4%; 95% CI, -13.8% to 11.5%; interaction P = .03).
Conclusions and relevance: The trial results suggest that, among adults 65 years or older, HD-IIV provided consistent benefit for cardiorespiratory, cardiovascular, and influenza hospitalizations compared with SD-IIV, regardless of diabetes status.
Trial registration: ClinicalTrials.gov Identifier: NCT05517174.
. 2026 Jan 12.
doi: 10.1001/jamainternmed.2025.7286. Online ahead of print. High-Dose vs Standard-Dose Influenza Vaccine in Older Adults With Diabetes: A Secondary Analysis of the DANFLU-2 Randomized Clinical Trial
Anne Bjerg Nielsen[SUP] 1 2 [/SUP], Niklas Dyrby Johansen[SUP] 1 2 [/SUP], Daniel Modin[SUP] 1 2 [/SUP], Matthew M Loiacono[SUP] 3 4 [/SUP], Rebecca C Harris[SUP] 5 [/SUP], Marine Dufournet[SUP] 6 [/SUP], Carsten Schade Larsen[SUP] 7 8 [/SUP], Lykke Larsen[SUP] 9 [/SUP], Lothar Wiese[SUP] 10 [/SUP], Michael Dalager-Pedersen[SUP] 11 12 [/SUP], Brian L Claggett[SUP] 13 [/SUP], Kira Hyldekær Janstrup[SUP] 1 2 [/SUP], Katja Vu Bartholdy[SUP] 1 2 [/SUP], Katrine Feldballe Bernholm[SUP] 1 2 [/SUP], Julie Inge-Marie Helene Borchsenius[SUP] 1 2 [/SUP], Filip Søskov Davidovski[SUP] 1 2 [/SUP], Lise Witten Davodian[SUP] 1 2 [/SUP], Maria Dons[SUP] 1 2 [/SUP], Lisa Steen Duus[SUP] 1 2 [/SUP], Caroline Espersen[SUP] 1 2 [/SUP], Frederik Holme Fussing[SUP] 1 2 [/SUP], Anne Marie Reimer Jensen[SUP] 1 2 [/SUP], Nino Emanuel Landler[SUP] 1 2 [/SUP], Adam Cadovius Femerling Langhoff[SUP] 1 2 [/SUP], Mats Christian Højbjerg Lassen[SUP] 1 2 [/SUP], Camilla Ikast Ottosen[SUP] 1 2 [/SUP], Morten Sengeløv[SUP] 1 2 [/SUP], Kristoffer Grundtvig Skaarup[SUP] 1 2 [/SUP], Manan Pareek[SUP] 1 2 [/SUP], Dirk Müller-Wieland[SUP] 14 [/SUP], Scott D Solomon[SUP] 13 [/SUP], Martin J Landray[SUP] 15 [/SUP], Gunnar H Gislason[SUP] 1 16 17 [/SUP], Lars Køber[SUP] 16 18 [/SUP], Pradeesh Sivapalan[SUP] 16 19 [/SUP], Cyril Jean-Marie Martel[SUP] 20 [/SUP], Jens Ulrik Stæhr Jensen[SUP] 16 19 [/SUP], Tor Biering-Sørensen[SUP] 1 2 18 21 [/SUP]
Affiliations
- PMID: 41525066
- DOI: 10.1001/jamainternmed.2025.7286
Importance: Influenza infection poses a substantial risk of severe complications, particularly in older adults and high-risk populations, such as individuals with diabetes. The high-dose inactivated influenza vaccine (HD-IIV) has demonstrated superior efficacy against influenza infection compared with the standard-dose inactivated influenza vaccine (SD-IIV) among adults 65 years or older. However, there is limited evidence on its effectiveness in preventing severe respiratory and cardiovascular outcomes in individuals with diabetes.
Objective: To investigate the relative vaccine effectiveness (rVE) of HD-IIV vs SD-IIV against severe respiratory and cardiovascular outcomes according to diabetes status and across diabetes subgroups.
Design, setting, and participants: This was a prespecified secondary analysis of DANFLU-2, a pragmatic, open-label, individually randomized clinical trial conducted in Denmark during the 2022/2023 to 2024/2025 influenza seasons. Adults 65 years or older were eligible for inclusion regardless of comorbidities. Data were obtained from nationwide health registries and analyzed from June to October 2025.
Interventions: Participants were randomly allocated 1:1 to receive HD-IIV or SD-IIV.
Main outcomes and measures: Outcomes included respiratory and cardiovascular hospitalizations. The potential effect modification by diabetes status and across diabetes subgroups was tested.
Results: Among 332 438 participants (mean [SD] age, 73.7 [5.8] years; 161 538 female individuals [48.6%]), 43 881 (13.2%) had diabetes. Overall, HD-IIV compared with SD-IIV was associated with reduced cardiorespiratory hospitalization, cardiovascular hospitalization, and influenza hospitalization. Effect estimates were similar for participants with and without diabetes for cardiorespiratory hospitalization (diabetes: rVE, 7.4%; 95% CI, -2.5% to 16.3%; no diabetes: rVE, 5.3%; 95% CI, 0.4%-10.0%; interaction P = .69), cardiovascular hospitalization (diabetes: rVE, 12.0%; 95% CI, -0.9% to 23.3%; no diabetes: rVE, 6.0%; 95% CI, -0.4% to 12.0%; interaction P = .38), and influenza hospitalization (diabetes: rVE, 41.6%; 95% CI, 5.0%-64.7%, vs no diabetes: rVE, 44.3%; 95% CI, 25.3%-58.7%; interaction P = .87). Duration of diabetes appeared to modify the effect of HD-IIV vs SD-IIV for cardiorespiratory hospitalization, with suggested benefit of HD-IIV in participants with diabetes duration longer than 5 years (rVE, 20.4%; 95% CI, 5.3%-33.1%), but not in those with shorter duration (rVE, -0.4%; 95% CI, -13.8% to 11.5%; interaction P = .03).
Conclusions and relevance: The trial results suggest that, among adults 65 years or older, HD-IIV provided consistent benefit for cardiorespiratory, cardiovascular, and influenza hospitalizations compared with SD-IIV, regardless of diabetes status.
Trial registration: ClinicalTrials.gov Identifier: NCT05517174.