Metformin Use before Influenza Vaccination May Lower the Risks of Influenza and Related Complications

Abstract

Older adults are more likely to have influenza and respond less well to the flu vaccine. We conducted this study to investigate whether pre-influenza vaccination metformin use had an effect on influenza and relevant complications in older adults with type 2 diabetes mellitus. Propensity score matching was used to identify 28,169 pairs of metformin users and nonusers from Taiwan’s National Health Insurance Research Database from 1 January 2000 to 31 December 2018. We used Cox proportional hazards models to calculate the risks of hospitalization for influenza, pneumonia, cardiovascular disease, ventilation, and mortality between metformin users and nonusers. Compared with metformin nonusers, the aHRs (95% CI) for metformin users at risk of hospitalization for influenza, pneumonia, cardiovascular disease, invasive mechanical ventilation, death due to cardiovascular disease, and all-cause mortality were 0.60 (0.34, 1.060), 0.63 (0.53, 0.76), 0.41 (0.36, 0.47), 0.56 (0.45, 0.71), 0.49 (0.33, 0.73), and 0.44 (0.39, 0.51), respectively. Higher cumulative duration of metformin use was associated with lower risks of these outcomes than no use of metformin. This cohort study demonstrated that pre-influenza vaccination metformin use was associated with lower risks of hospitalizations for influenza, pneumonia, cardiovascular disease, mechanical ventilation, and mortality compared to metformin nonusers.

Metformin use before COVID-19 vaccination and the risks of COVID-19 incidence, medical utilization, and all-cause mortality in patients with type 2 diabetes mellitus

“…Diaz et al have demonstrated that metformin could induce 5’- adenosine monophosphate-activated protein kinase (AMPK) phosphorylation in B cells, increase the percentages of circulating switched memory B cells, decrease the pro-inflammatory exhausted memory B cells, decrease B cell-intrinsic inflammation, and improve the in vivo and in vitro antibody response to the influenza vaccine [18] . Our recent study also revealed that pre-influenza vaccination metformin use could reduce the risk of influenza infection in older people with type 2 DM [19] . However, the present study showed that the use of metformin 60, 120, or 180 days before COVID-19 vaccination did not reduce the incidence of COVID-19, and we showed similar results among patients with different ages, sex, ethnic groups, and vaccines, with or without diabetic complications, and insulin use or nonuse.…”

“…Previous studies have shown that metformin significantly reduces the risk of cardiovascular diseases, pneumonia, sepsis, herpes zoster, and post-herpetic neuralgia in patients with type 2 diabetes [23] , [13] , [14] , [15] . The pre-influenza vaccination use of metformin significantly lowered the risk of hospitalization for influenza, pneumonia, mechanical ventilation, and mortality compared to metformin nonusers in older patients with type 2 DM [19] . A meta-analysis and systemic review showed that metformin use was associated with a 27% lower risk of hospitalization for COVID-19 than metformin no-use [16] .…”

“…Metformin could attenuate intrinsic B-cell inflammation and enhance the in vitro and in vivo antibody response to influenza vaccines in obese patients with type 2 DM [18] . Our previous study showed that metformin use before influenza vaccination could reduce the risks of influenza and complications [19] . Therefore, we designed this study to investigate whether metformin use before COVID-19 vaccination affects risk of COVID-19 incidence, medical utilization and mortality.…”

Preparing for the next viral threat with broad-spectrum antivirals

“…Metformin reduced morbidity and mortality in mice infected with DENV and IAV, but not ZIKV ( 168 , 169 ). Diabetic patients on metformin treatment were found to have lower morbidity and mortality upon influenza virus infection ( 170 ) and a trend toward reduced mortality when infected with SARS-CoV-2 ( 171 ). Contrastingly, metformin showed no clinical benefit in nondiabetic COVID-19 patients ( 172 ).…”

Old drug, new tricks: the utility of metformin in infection and vaccination responses to influenza and SARS-CoV-2 in older adults

“…Retrospective studies suggest metformin can improve vaccine-induced protection in humans as well. Diabetics on metformin prior to flu vaccination had a lower risk of severe flu infection and associated complications compared to diabetics not on metformin ( Yen et al, 2022 ). More specifically, the risk of hospitalization for influenza, pneumonia, cardiovascular disease, invasive mechanical ventilation, death due to cardiovascular diseases, and all-cause mortality in older adults with T2D was decreased after contracting flu when participants were taking metformin prior to vaccination ( Yen et al, 2022 ).…”