Patients with diabetes who take Actos should be aware of the Actos cancer risk.

Actos (pioglitazone) is prescribed to patients who need medication to lower their blood sugar, which is often high in patients with type-2 diabetes. Even though the pancreas of a type-2 diabetes patient continues to produce insulin, the body is unable to sufficiently use it. Patients might not know about the Actos cancer risk until it’s too late.

Actos and competitor Avandia are in a class of drugs known as thiazolidinedione (TZD) that reduce insulin resistance by activating a receptor inside the cells to deter insulin resistance. The receptor specifically is called the peroxisome proliferator-activated receptor (PPAR).

Both Actos and Avandia became available in the 1990s. Even though they are in the same class of drugs, Avandia has not shown the same side effects as Actos.

A 2005 clinical trial revealed Actos patients were being diagnosed with bladder cancer at an increased rate. Other studies have confirmed this risk.

In 2016, researchers in Canada determined the Actos cancer risk increases in relation to the amount of time the patient takes the medication. The March 30, 2016 issue of the BMJ published the study that indicated the risk of bladder cancer increases in patients who take the drug longer than two years or the equivalent of more than 28,000 milligrams in their lifetime.

They analyzed more than145,000 patients who received Actos between the years 2000 and 2013. One researcher said the Actos cancer risk increases as the drug accumulates in the body.

Actos Cancer Risk Unique

The increased risk of bladder cancer appears to be unique with Actos because Avandia patients did not exhibit a similar increased incidence of cancer.

Researchers say that even though Actos and Avandia are in the same drug class, there is a key difference. Avandia works on one receptor to prompt better insulin absorption, but Actos actually works on two receptors.

Takeda Pharmaceuticals makes Actos, and lawsuits have alleged the drug company knew in 1996 of the Actos cancer risk. Back then, Takeda’s researchers conducted a study that found rats and mice developed abnormal bladder cells and tumor formation after taking Actos. The abnormal bladder cells allegedly could lead to cancer.

At that time, Takeda purportedly asked Dr. Sam Cohen of the University of Nebraska Medical Center to hypothesize a reason the Actos cancer risk found in rodents did not apply to humans. He obliged by formulating the “Cohen hypothesis,” which blamed urine crystal production found exclusively in male rats to explain why rats were at an increased risk of bladder cancer from Actos. (The Cohen hypothesis would later be debunked.)

Unfortunately, his hypothesis was one of the reasons the FDA approved Actos in 1999, although records indicate one FDA reviewer voiced problems with the Cohen hypothesis.

The FDA began a closer examination of Actos cancer risk in 2002, but Takeda would not amend its stance that the risk was non-existent until 2010. Finally, in 2011, Takeda added a warning to the Actos label that the drug could cause an increased risk of bladder cancer.

In 2015, Takeda agreed to a $2.4 billion Actos bladder cancer settlement in an MDL that settled almost 9,000 claims made by patients and family members.