Diabetes Metab Res Rev. 2017 Dec 22. doi: 10.1002/dmrr.2975. [Epub ahead of print]
Is Metformin Poised for a Second Career as an Antimicrobial?Malik F1, Mehdi SF1, Ali H1, Patel P1, Basharat A1, Kumar A1, Ashok F1, Stein J1, Brima W1, Malhotra P1,2, Roth J1,3. Author information 1Laboratory of Diabetes and Diabetes-related Research, Feinstein Institute for Medical Research, Manhasset, NY, United States.2Division of Infectious Diseases.3Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY, United States.
AbstractBACKGROUND: Metformin, a widely used anti-hyperglycemic, has a good safety profile, reasonably manageable side-effects, is inexpensive and causes a desirable amount of weight loss. In four studies of patients with tuberculosis (one prospective and three retrospective), metformin administration resulted in better outcomes. In mice with several models of endotoxemia, metformin diminished levels of pro-inflammatory 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 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 for 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.
METHODS: A systematic review was done of PubMed indexed articles that examined the effects of metformin on a wide range of pathogens.
RESULTS: 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 Trichinella spiralis, Staphylococcus aureus, Pseudomonas 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 of multiple infectious diseases.