Conventional drugs used to treat TB usually adopt a pathogen-targeted strategy which attacks and kills bacteria directly. This approach has caused Mtb strains to acquire drug resistance, making existing treatments become increasingly ineffective and resulting in a pressing need to design new therapeutic strategies for the disease.

An international team of scientists led by the Singapore Immunology Network (SIgN), a research institute under the Agency for Science, Technology and Research (ASTAR), Singapore began searching for drugs that could control Mtb replication indirectly. They screened FDA-approved drugs and identified Metformin (MET), an old anti-diabetic drug that could defend Mtb invasion without targeting the bacteria directly. Instead, MET targets the host cells to trigger the production of a chemical which then damages Mtb and stops its replication.
Such indirect, host-targeted approach is less likely to engender drug resistance. The team also discovered that MET improves the efficacy of conventional anti-TB drugs when used in combination with them. The scientists then validated the findings with patient data provided by the Tuberculosis Clinical Unit at the Tan Tock Seng Hospital, and consequently verified that the use of MET is indeed associated with improved TB control and decreased disease severity.
This anti-diabetic drug is therefore a promising adjunctive therapy that could enhance the effectiveness of existing TB treatments.
As it is a drug that is currently in use, another benefit of using MET as an adjunct treatment for TB is that it is likely to shorten the time required for clinical trials.

"Using MET as an adjunct treatment for TB is very promising since this drug interferes with the biochemical pathway essential for the bacteria's survival and does not promote the development of drug resistance," said lead scientists Dr Amit Singhal, Project Leader and Prof Gennaro De Libero, Principal Investigator at SIgN.
"MET is also a very cheap and safe drug with no adverse effect on non-diabetic patients. This would likely shorten clinical trials and we are confident that a better and affordable TB treatment will be made available soon," said Singhal.

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