Two very popular and enormously successful diabetes drugs have come under intense regulatory scrutiny over the past year. Avandia and Actos were developed and prescribed to treat type 2 diabetes. In people with type 2 diabetes the body does not make enough insulin, and the insulin that the body produces does not work as well as it should. The body can also make too much sugar. When this happens, sugar (glucose) builds up in the blood. The main goal of treating diabetes is to lower blood sugar to a normal level. Type 2 diabetes is the most common form.
Both Avandia and Actos are in a class of drugs known as thiazolidinedione (TZD). Last fall, the prescribing of Avandia was severely restricted in the U.S. because of concerns about an increased risk of heart attack. After issuance on an FDA Safety Alert regarding Avandia linking the drug to an abnormally high risk of heart attack the use of Avandia has basically ceased. Quick to capitalize on Avandia’s troubles, Actos was touted as a safer alternative for the treatment of patients’ diabetes.
It now appears that Actos is certainly not a safer alternative for diabetes sufferers. Actos has recently been linked to the development of bladder cancer making it the second medication in the thiazolidinedione (TZD) class to be associated with serious side effects within the past year. Patients taking the diabetes drug Actos for more than a year may have an increased risk of bladder cancer, according to an FDA interim review of an ongoing epidemiological study. The warning comes just days after two European countries banned use of the drug. The European Medicines Agency (EMA) has yet to release any guidance on use of Actos. Five-year data show that although there’s no overall increased risk of bladder cancer, patients with the longest exposure to and the highest cumulative dose of the drug were at greater risk, the agency said.
Researchers who discovered the link believe that this data, coming on the heels of the Avandia disaster may lead doctors to simply quit prescribing any drug in the thiazolidinedione (TZD) class.
This is especially true since there appear to be safer alternatives. At least two alternative therapies have not been shown to-date to cause serious or life threatening side effects. Byetta (exenatide) and Januvia (a DPP-4 inhibitor or sitagliptin) seem to be a reasonable alternative given the risk of major, life threatening side effects with the use of Avandia or Actos from the thiazolidinedione (TZD) class. Dr. Albert Levy of Mount Sinai School of Medicine in N.Y. has been quoted as saying, “I will ask my patients on Actos to consider dropping it and give them an alternative.” A third potential alternative, Victoza (GLP-1 agonist or liraglutide) unfortunately has been recently linked by the FDA to the development of Thyroid cancer and pancreatitis.
Actos is manufactured by Takeda Pharmaceuticals and generated sales of over $2.4 billion dollars in 2008. Prior to the FDA’s warning, Actos did not contain any caution or warning about cancer risk in its packaging or labelling. The FDA has now demanded that Takeda include that warning in Actos’ label.
This new safety information is based on the FDA’s review of a study of 200,000 diabetic patients with Type 2 diabetes. The study found that diabetics who took Actos for more than a year had a 40% higher risk of developing bladder cancer.
The FDA admitted in its announcement that it was also aware of a recent study from France that led to these drugs being banned in France and Germany. The drug is also scheduled to be recalled in New Zealand.