Reply

In Response: We thank the letter authors for their interest in our work (1). Their point regarding the use of metformin and lactic acidosis is well taken. Their suggestions are useful because they address a very important safety issue, which may influence future clinical studies involving metformin.

The results of the systematic review of the Cochrane Collaboration and in particular the lack of evidence supporting an association between metformin use and risk of lactic acidosis have been reported (2). Because of the ongoing scientific debate about this issue, we agree that consideration should be about potential adverse events related to metformin use, in particular potentially lethal events. Thus, we considered it important to mention the possible association between metformin use and lactic acidosis in our article for a number of reasons. First, we are using metformin for the first time in nondiabetic cancer patients, a population in which data on metformin side effects have not been reported. Second, this is important because of the potential use of metformin in prevention trials involving healthy, high-risk individuals. Third, some publications have reported an association between lactic acidosis and clinical conditions such as electrolytic unbalance. This observation is important because vomiting and diarrhea are known to occur during metformin treatment, in addition to liver or renal insufficiency (3).

Despite these cautions, the potential to use metformin in a clinical setting in nondiabetic patients with cancer and in high-risk subjects for preventive purposes is worthy of further investigation.