# A Mathematical Model of Metformin Action on COVID-19 Risk Infection in Cardiovascular Diabetic Patients Studied by FTIR Spectroscopy

**Authors:** Evangelos Mylonas, Christina Mamareli, Michael Filippakis, Ioannis Mamarelis, Jane Anastassopoulou, Theophile Theophanides

PMC · DOI: 10.3390/ijms26136332 · International Journal of Molecular Sciences · 2025-06-30

## TL;DR

This study uses a mathematical model and FTIR spectroscopy to show that metformin may reduce the risk of severe COVID-19 in diabetic patients.

## Contribution

A novel mathematical model and FTIR-based diagnostic frequencies are used to explain metformin's protective effect against COVID-19.

## Key findings

- The band at 1775 cm−1 in FTIR spectra is a diagnostic frequency for IgG antibodies in COVID-19 infection.
- Metformin reduces AGE production and interacts with the SARS-CoV-2 spike protein, potentially preventing viral entry.
- Thiazolidinediones increase the risk of severe COVID-19 compared to metformin and insulin.

## Abstract

Several studies have revealed that patients with type 2 diabetes (T2D) infected with COVID-19 who were medicated with metformin showed higher recovery rates than those administered other antidiabetic drugs. To determine the mechanism of action of antidiabetic drugs against COVID-19, we developed a mathematical model that was based on the number of infected and recovered T2D patients. Moreover, the “diagnostic frequencies” of the infected T2D patients, determined using Fourier-Transform Infrared (FTIR) spectroscopy, were very helpful. In particular, the band at 1775 cm−1, attributed to IgG antibodies, could be used as a “diagnostic frequency” for COVID-19 infection. The increased intensity of the band of vC-O-C sugar moieties suggests an increased number of OH chemical groups that enhance the binding sites of SARS-CoV-2 spike protein for entering host cells. The changes were more pronounced in patients medicated with thiazolidinediones than those using insulin and metformin. Both FTIR spectra and the developed mathematical model confirmed that patients using thiazolidinediones showed a higher risk of COVID-19 infection and mortality. The data support the hypothesis that the NH chemical groups of metformin molecules interact directly through the SARS-CoV-2 spike protein, preventing the entry of COVID-19 into the host membrane cells. Indirectly, metformin inhibits the host binding sites for COVID-19 entry by lowering AGE production.

## Linked entities

- **Chemicals:** metformin (PubChem CID 4091), AGE (PubChem CID 7838)
- **Diseases:** type 2 diabetes (MONDO:0005148), COVID-19 (MONDO:0100096)

## Full-text entities

- **Genes:** INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}
- **Diseases:** T2D (MESH:D003924), COVID-19 (MESH:D000086382), Infection (MESH:D007239), Diabetic (MESH:D003920)
- **Chemicals:** AGE (MESH:D017127), vC-O-C sugar (-), OH (MESH:C031356), Metformin (MESH:D008687), thiazolidinediones (MESH:D045162)
- **Species:** Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12249686/full.md

## References

39 references — full list in the complete paper: https://tomesphere.com/paper/PMC12249686/full.md

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Source: https://tomesphere.com/paper/PMC12249686