Abstract
Tuberculosis (TB) disease is an international health concern caused by the bacteria Mycobacterium tuberculosis (Mtb). Evolution of multi-drug-resistant strains may cause bacterial persistence, rendering existing antibiotics ineffective. Hence, development of new or repurposing of currently approved drugs to fight Mtb in combination with existing antibiotics is urgently needed to cure TB which is refractory to current therapy. The shortening of TB therapy and reduction in lung injury can be achieved using adjunctive host-directed therapies. There is a wide range of probable candidates which include numerous agents permitted for the treatment of other diseases. One potential candidate is metformin, a Food and Drug Administration (FDA)-approved drug used to treat type 2 diabetes mellitus (DM). However, there is a scarcity of evidence supporting the biological basis for the effect of metformin as a host-directed therapy for TB. This scoping review summarizes the current body of evidence and outlines scientific gaps that need to be addressed in determining the potential role of metformin as a host-directed therapy.
Highlights
Tuberculosis (TB), largely a curable disease, remains the leading cause of mortality globally, fueled by the unprecedented increase in anti-mycobacterial drug resistance
Reviewed published literature supports a biologic basis for the use of MET as Host-directed therapy (HDT) for Mycobacterium tuberculosis (Mtb) infection (Alisjahbana et al, 2007)
This review suggests that MET has the potential to improve existing shortfalls of current TB therapy (Figure 2)
Summary
Tuberculosis (TB), largely a curable disease, remains the leading cause of mortality globally, fueled by the unprecedented increase in anti-mycobacterial drug resistance. 558,000 were new cases resistant to rifampicin–a key drug in the current first-line treatment. Eighty-two percent of the rifampicin-resistant cases had multi-drug-resistant TB (MDR-TB), which includes, at a minimum, resistance to the first line drug isoniazid (World Health Organization, 2018). While the incidence of drug resistance is approximately 5% of total TB cases, 17% of TB deaths were due to drug-resistant strains (World Health Organization, 2018). Treatment regimens for TB consist of combinations of anti-mycobacterial drugs aimed at eradicating infection while preventing the development of resistance and recurrent infection. AntiTB regimens are lengthy and associated with high toxicity, driving poor treatment adherence and development of MDR and extensively drug-resistant (XDR) TB (Shenoi et al, 2009; Calver et al, 2010; Zumla et al, 2013; Millington, 2018).
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