According to Dr. Nissen, “the FDA needs to begin to think more clearly about these kinds of risky situations and act earlier.”
Dr. Meyer said that the FDA would not exclude any regulatory action at this point, and an advisory board committee meeting could take place in the next few months.
The investigators said their results led them to question “the appropriateness of the current regulatory pathways for the development of drugs to treat diabetes,” a sentiment that was echoed in the editorial.
“Rosiglitazone was approved on the basis of short-term studies of the surrogate end point of glycemic control,” Dr. Psaty and Dr. Furberg wrote.
But the underlying assumption that high levels of glycated hemoglobin increase risk and that a reduction in this measure will improve health outcomes “ignores the many actions of the genes activated by PPAR-γ agonists, only some of which are currently known. Many physicians did not require proof of health benefits as a criterion for selecting rosiglitazone as a therapy for type 2 diabetes,” they added.
Rosiglitazone potentially could contribute to the risk of MI by increasing LDL cholesterol levels or modestly reducing hemoglobin levels, which could provoke ischemic events in those with heart failure, the investigators said.
Dr. Richard Hellman, president of the American Association of Clinical Endocrinologists, noted that glitazones probably affect more than 100 human genes. “When an agent is so active at the gene level, postmarketing studies need to address the issue of special populations,” said Dr. Hellman, clinical professor of medicine, University of Missouri, Kansas City. The findings “provide more ammunition for increased caution” in prescribing rosiglitazone.
'The FDA needs to begin to think more clearly about these kinds of risky situations and act earlier.' DR. NISSEN