TABLE 1.
Examination of the impact of metformin on SARS-CoV-2 infection models.
| Author, year | Study design | Substrate | Key findings |
|---|---|---|---|
| Bramante et al. (2023) | In vivo (randomized trial) | COVID-19 patients | Metformin demonstrated a possible benefit in preventing more severe outcomes such as emergency department visits, hospitalization, or death |
| Carolyn et al. (2023) | In vivo (randomized trial) | COVID-19 patients | Metformin showed a 42% reduction in ER visits/hospitalizations/death through 14 days and a 58% reduction in hospitalizations/death through 28 days. Furthermore, metformin demonstrated a 42% reduction in Long COVID through 10 months. Viral load analysis revealed a 3.6-fold reduction with metformin compared to placebo |
| Sun et al. (2022b) | In vitro experimental study | Human airway epithelial cell lines (BEAS2B, A549, and 16HBE) | Metformin exhibited multifaceted effects, including restoration of autophagy, suppression of pyroptosis, and attenuation of inflammatory response |
| Parthasarathy et al. (2022) | In vitro experimental study | Calu3 (respiratory epithelial cell line) and Caco2 (gut epithelial cell line) | Metformin pretreatment effectively suppressed viral replication and protein expression in both respiratory and gut epithelial cell lines |
| Ventura-López et al. (2022) | In vitro experimental study | H1299 and Vero E6 cell lines | Metformin glycinate demonstrated significant reduction in viral load and enhanced cell viability against different SARS-CoV-2 variants |
| Mercado-Gómez et al. (2022) | In vitro experimental study | Human primary hepatocytes, human upcyte second-generation hepatocytes, humanized ACE2 (hACE2) mice, and wild-type mice | Metformin exhibited hepatoprotective effects by suppressing ACE2 expression, reducing viral infection rates, and modulating inflammatory markers in hepatocytes |
| Cory et al. (2021) | In vitro experimental study | Purified classical monocytes from healthy human subjects | Metformin pretreatment resulted in the suppression of glycolytic response and downregulation of pro-inflammatory cytokines upon viral exposure |
| Chen et al. (2021) | In vitro and in vivo assays | In vivo: Midbrain dopaminergic neurons derived from H9 human embryonic stem cells injected into mice. In vitro: Midbrain dopaminergic neuron cell line derived from human pluripotent stem cells | Metformin exhibited antiviral effects by reducing viral RNA levels and preventing cellular senescence in midbrain dopaminergic neurons |
| Schaller et al. (2021) | Ex vivo and in vitro assays | Cryopreserved bank of human lung tissue and Vero E6 cell line | Metformin exhibited variable efficacy, with significant reduction in SARS-CoV-2 titers observed in lung tissues but not in Vero E6 cell line |
| Xian et al. (2021) | In vitro and in vivo assays | Bone marrow–derived macrophages from nondiabetic mice | Metformin displayed immunomodulatory effects by inhibiting NLRP3 inflammasome activation, cytokine production, and mitochondrial dysfunction |
| Gordon et al. (2020) | In vitro experimental study | Vero E6 cell line | Metformin demonstrated potent antiviral activity by inhibiting viral replication and promoting cellular viability |