Comorbid type 2 diabetes poses a great challenge to the global control of tuberculosis. Here we assessed the efficacy of metformin (MET); an anti-diabetic drug, in mice infected with a very-low dose of Mycobacterium tuberculosis. In contrast to diabetic mice, infected non-diabetic mice that received the same therapeutic concentration of MET presented with significantly higher disease burden. This warrants further studies to investigate the disparate efficacy of MET against tuberculosis in diabetic and non-diabetic individuals.