Is metformin poised for a second career as an antimicrobial?

Metformin, a widely used antihyperglycaemic, has a good safety profile, reasonably manageable side-effects, is inexpensive, and causes a desirable amount of weight loss. In 4 studies of patients with tuberculosis (1 prospective and 3 retrospective), metformin administration resulted in better outcomes. In mice with several models of endotoxemia, metformin diminished levels of proinflammatory cytokines and improved survival. Laboratory studies showed effectiveness of the drug on multiple pathogens, including Trichinella spiralis, Staphylococcus aureus, Pseudomonas aeruginosa, hepatitis B virus, hepatitis C virus, and human immunodeficiency virus. Metformin administration in humans and mice produced major changes in the composition of the gut microbiota. These recently discovered microbe-modulating properties of the drug have led investigators to predict wide therapeutic utility for metformin. The recent easing in United States Food and Drug Administration (FDA) guidelines regarding administration of metformin to patients with kidney disease, and reduced anxiety about patient safety in terms of lactic acidosis, increase the probability of broadening of metformin's usage as a treatment of infectious agents. In this text we review articles pertinent to metformin's effects on microorganisms, both pathogens and commensals. We highlight the possible role of metformin in a wide range of infectious diseases and a possible expansion of its therapeutic profile in this field. A systematic review was done of PubMed indexed articles that examined the effects of metformin on a wide range of pathogens. Metformin was found to have efficacy as an antimicrobial agent in patients with tuberculosis. Mice infected with Trypanosomiasis cruzi had higher survival when also treated with metformin. The drug in vitro was active against T. spiralis, S. aureus, P. aeruginosa, and hepatitis B virus. In addition there is emerging literature on its role in sepsis. We conclude that metformin may have a potential role in the therapy for multiple infectious diseases. Metformin, in addition to its traditional effects on glucose metabolism, provides anti-microbial benefits in patients with tuberculosis and in a very wide range of other infections encounters in vitro and in vivo.