Despite its array of benefits that comparatively outweigh alternative oral anti-glycaemic agents, the ability of clinicians to prescribe metformin is restricted. There are numerous contra-indications and cautions concerning the putative risks of metformin-related side effects that necessitate cessation of metformin. Notably the often stated, yet completely unsubstantiated, heightened risk for development of lactic acidosis in the context of renal insufficiency or a kidney transplant is particularly contentious. In this article, I will critique current regulatory advice and argue for further research to evaluate the safety and efficacy of metformin use in populations where the benefits of metformin are likely to far outweigh any infinitesimal risk (such as advanced chronic kidney disease and those after kidney transplantation). The only way to settle this debate is for well-designed trials and registry analyses to ascertain the safety and efficacy of metformin in these ‘high-risk’ populations. That is what evidence-based medicine demands and unfortunately is long overdue.