Objective: Metformin, a first-line agent for type 2 diabetes mellitus (T2DM) has been shown to have immunomodulating properties in vaccine efficacy, aging and infections, including pneumonia. This study evaluated whether metformin-use associated with lower risk for invasive pneumococcal disease (IPD) post receipt of a pneumococcal vaccine (PNV).

Methods: This was a retrospective U.S. cohort analysis of a third-party medical and pharmacy claims database from 2009 to 2019. Adults 18 years of age and older who received a PNV and were continuously enrolled for more than 1 year before and after PNV administration were included. Diagnosis of IPD requiring hospitalization was determined using ICD-9/10-CM codes. Metformin-use was defined as more than 90 days of claim with fill within 30 days prior to PNV. Demographics, PNV type/year, medications, and co-morbidities were covariates. Multivariable logistic-regression models were conducted, stratified by metformin-use and T2DM.

Results: Overall, 600,132 adults were included. The median age was 65 years and 45.1% were males. Approximately 24% of individuals with T2DM (n=155,308) were metformin-users compared to 1.6% of those without T2DM (n=444,824). Metformin-use was independently associated with lower risk of IPDs post-PNV (aOR 0.878, 95% CI 0.826-0.933). This protective effect was likely driven by individuals with T2DM using metformin vs. non-users (aOR 0.812, 95% CI 0.760-0.867). In contrast, among those without T2DM, there were no differences in IPD (aOR 0.989, 95%CI 0.852-1.148). The median (IQR) days to event was shorter post-PNV among metformin-users vs. non-users [495 (276-870) vs. 548 (276-1170), p<0.001].

Conclusion: Metformin-use was associated with a reduced risk of IPDs after receiving PNVs, particularly among those with T2DM. These results add to the sparse data highlighting the immunomodulatory effects of metformin and its potential role in vaccine-care, aging and preventative medicine.