**4.3 Metformin (Biguanides)**

Metformin, a biguanide drug approved for glycaemic control in patients suffering from Type II diabetes mellitus, falls within the group of host-directed therapies against TB. Multiple adjunctive activities have been investigated. *In vitro* studies have shown a potentiation of the standard TB drugs, an increased immune response and mediation of phagosome-lysosome fusion. The phagolysosome fusion leading to the inhibition of bacterial growth is due to the expression of AMP-activated protein kinase, which in turn increases the production of mitochondrial reactive oxygen species (mROS) [38, 39]. The adjunctive properties and potential in TB treatment have been captured in two reviews [40, 41]. A phase II clinical trial investigating the safety and tolerability of metformin in TB/HIV patients is yet to start, and the investigation is planned to be completed in 2024.
