Should metformin be our antiglycemic agent of choice post-transplantation?

New onset diabetes after transplantation (NODAT) is a major complication associated with solid-organ transplantation, sharing many similarities with type 2 diabetes mellitus. While metformin is recommended as the antiglycemic agent of choice in the general population, guidelines post-transplantation do not endorse metformin with equal importance and promote meglitinides as the agents of choice. Concerns with tolerability and safety of metformin in the complex polypharmacy of transplant recipients are likely causative factors for reluctant prescription among clinicians. However, such practice denies recipients a wide array of benefits attributed to metformin use in the general population. These include attenuation of abnormal glucose metabolism (diabetes treatment and prevention), weight neutrality, improvement in pathophysiological components of the metabolic syndrome (insulin resistance, subclinical inflammation, endothelial dysfunction and nonalcoholic fatty liver disease [NAFLD]), lipid-lowering properties, cardiovascular protection and antineoplastic potential. Whether such benefits translate from the general population to our high-risk recipients requires further investigation. By discussing the evidence of the risk/benefit ratio of metformin, the aim of this article is to promote the safe use of metformin as the first-line antiglycemic agent in the context of solid-organ transplantation for a host of indications that require clinical validation with appropriately designed trials.