Old Diabetes Drug Takes On New Target

Scientists have found that the drug metformin can indirectly boost existing TB therapy while avoiding drug resistance.

AsianScientist (Dec. 23, 2014) – A drug commonly used to treat diabetes can also be used to boost the efficacy of tuberculosis (TB) treatment, without causing drug resistance. The study documenting these findings has been published in Science Translational Medicine.

TB is an air-borne infectious disease caused by a bacterium called Mycobacterium tuberculosis (Mtb), which often infects the lungs. Even though drugs are available to treat the disease, TB continues to be a major threat to public health, killing close to 1.5 million people every year.

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 increasingly ineffective and resulting in a pressing need to design new therapeutic strategies for the disease.

The team of scientists led by Singapore Immunology Network (SIgN), a research institute under the Agency for Science, Technology and Research (A*STAR), 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.

“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. 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 lead scientists Dr. Amit Singhal and Professor Gennaro De Libero, from SIgN.

Professor Wang Yee Tang, Senior Consultant of Tan Tock Seng Hospital’s Tuberculosis Control Unit, added, “Today, we are using the same standard TB treatment which was introduced more than 40 years ago. New and better treatment strategies such as this MET adjunctive therapy will definitely be welcomed by TB physicians and patients. It is also important that we continue to protect the few TB drugs we have and prevent drug resistance from emerging.”

The article can be found at: Singhal et al. (2014) Metformin as Adjunct Antituberculosis Therapy.


Source: A*STAR; Photo: NIAID/Flickr/CC.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

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