Indeed, it is important for the FDA to warn the health care community and patients alike of potential medication risks. However, one wonders whether the FDA's current statement about Actos is helpful or confusing. The statement is based on statistical subanalysis, posing the question of whether it is a real finding or a result of “mining the data.” One must admit that unless the patient is a rat, the data seem to be very weak.
The FDA states that the bladder cancer risk with Actos increased with “higher doses” for a “longer duration.” Could one interpret that to mean lower dosages for a longer time are safe? Perhaps.
When TZDs first came to the market, many people used their highest doses. However, since recognizing their effects of weight gain, fluid retention, and CHF, most people continued usage on lower dosages, i.e., 15 mg or 30 mg for Actos. One of the reasons the FDA cited to severely restrict the usage of Avandia (rosiglitazone) was the presence of a safer alternative in the class, namely Actos.
So, what is the implication for clinical practice? I suggest that at this point we have no reason to stop using Actos. We surely have to continue to be careful in people who are at a high risk of developing bladder cancer, hence following an established precaution on the drug usage. As Actos is now, practically speaking, the sole available drug in the class and will soon be available as a generic, we can anticipate a further increase in its use. I believe in the important role of TZDs in the control of hyperglycemia of diabetes, especially in combination with metformin and incretin-based therapy, which would allow for a lower dose. I therefore suggest that we continue to use Actos at a dose not to exceed 30 mg, and calm our patients as to its perceived safety until further clarification from the FDA.
Dr. Handelsman is medical director and principal investigator of the Metabolic Institute of America.