Repurposing of Metformin for the prevention and treatment of Tuberculosis

Abstract

The bidirectional relationship between tuberculosis (TB) and diabetes mellitus (DM) is a major concern for medical professionals and epidemiologists as DM affects the severity, progress and outcome of TB and vice versa. Patients affected with TB have a higher rate of morbidity, treatment failure and mortality. Likewise, DM triples the risk of contracting TB and therefore poses a threat to the progress made in the reduction of TB incidence. Hence, it is pivotal to address both the diseases keeping in mind the each other. It is known that adjunct therapy with immunomodulatory drugs can enhance TB immunity among diabetic patients. Metformin, a commonly used anti-diabetic drug with adenosine monophosphate-activated protein kinase (AMPK) activation property, has shown the capacity to reduce the growth of Mycobacterium tuberculosis within the cell. This drug inhibits the mitochondrial complex and possesses antiinflammatory action. Therefore, Metformin can be considered as an ideal molecule for hostdirected or host-targeted therapy for TB.

Improving the treatment of bacterial infections caused by multidrug-resistant bacteria through drug repositioning

“…It has also been shown that in the case of tuberculosis, the use of metformin inhibits cell necrosis and contributes to tissue regeneration ( Guler and Brombacher, 2015 ). Metformin also promotes autophagy in infected macrophages and limits the development of mycobacteria by positively influencing the production of reactive oxygen species ( Vyas et al, 2022 ). For this reason, the molecule is currently in clinical trials for the treatment of tuberculosis (NCT05215990, NCT04930744).…”

“…The antibacterial mechanism of antidiabetic anh hypolipemic drugs is shown in Figure 8 ( Brown, 2015 ; Brindha et al, 2016 ; Guerra-De-Blas et al, 2019 ; Evans and McDowell, 2021 ; Vyas et al, 2022 ).…”