Potential Risks of Metformin in Transplant Patients

To the Editor:

Dr. Sharif's recent article was an excellent review of the benefits of metformin based on data in the general population, but did not adequately discuss how individual characteristics of the transplant patient might affect that decision, particularly in the immediate posttransplant setting (1). For example, while lactic acidosis with metformin has not been significant in the general population, it is not well studied after transplant where risk for lactic acidosis, overall, is higher due to a greater prevalence of renal insufficiency and sepsis, among other causes. The FDA, in fact, recommends that metformin be discontinued during any hospitalization, for 48 h after any contrast procedure, with any significant infection, as well as with heart failure and renal insufficiency. For these reasons, metformin may not be the drug of choice at the outset of diagnosis as new onset diabetes often occurs in the first few months after transplant, not uncommonly during a hospitalization, where these factors are mostly likely to be relevant. Also relevant to the decision is that metformin alone is less likely to be able to effectively control blood sugars in the hospitalized patient, particularly when the patient is on higher doses of immunosuppressant medications. In fact, significant hyperglycemia in the hospital is usually treated first with insulin with a plan to transition to one or more oral agents, including metformin, only if insulin requirements are relatively small, there is no active infection or planned contrast procedures, and the patient has adequate renal function. Specifically, metformin is contraindicated in men with serum creatinine >1.5 mg/dL and women with serum creatinine >1.4 mg/dL based on FDA recommendations
(http://www.fda.gov/ohrms/dockets/dailys/02/May02/053102/80047964.pdf). Even if metformin is effective initially, it may have to be withdrawn temporarily or permanently if renal function declines over time. Thus, although metformin is a valuable treatment option for the group as a whole, it may not be the best choice for treatment at the outset of diabetes after transplant, will likely need to be accompanied by other agents to achieve effective glucose control in many, and may need to be withdrawn frequently or permanently based on the risk factors identified in the transplant patient over time.

Disclosure

The author of this manuscript has no conflicts of interest to disclose as described by the American Journal of Transplantation.