When the oral diabetes drug Actos was released in 1999, it was lauded as a safer way to lower blood sugar and get Type 2 diabetes under control. But more than a decade later, numerous people have suffered a serious side effect of the drug: congestive heart failure.
The Actos heart failure risk is so profound that the drug now carries the U.S. Food and Drug Administration’s (FDA) stringent black-box warning, which underscores the significant chance of developing the condition in patients with or without pre-existing heart problems.
There is increasing evidence that the risk of taking Actos and developing CHF or having a heart attack is much greater than previously thought. Moreover, the maker of Actos, Takeda Pharmaceuticals, has been accused of concealing, or downplaying, the number and the severity of heart problems linked to Actos.
Clinical trials and other studies show that Actos carries a definitive link to users developing congestive heart failure. This dangerous side effect caused some people to file lawsuits against Takeda, which makes and markets the Type 2 diabetes drug.
Actos Linked to Heart Failure Problems From the Start
Actos is a member of the controversial thiazolidinedione (TZD) drug family, which has been known to cause heart problems. When Takeda ran clinical trials on the drug before its release, results showed a definitive link to heart failure.
In one clinical trial, 5,238 patients were treated with Actos or a placebo. According to the trial, a larger percentage of Actos patients experienced a “serious heart failure event” than those taking the placebo. The incidence of death from heart failure was also significantly higher in the Actos patients. Despite early clinical study findings that linked the drug’s use to the development of heart problems and bladder cancer, Actos was released to the market.
One of the side effects associated with Actos is edema, the accumulation of fluids in the body. When heart failure occurs, the body becomes congested with fluids and major organs begin to shut down. Fluids then build up in the tissues, lungs, liver and extremities. Because Actos is already known to cause edema, the extra buildup of bodily fluids can intensify heart problems. This further complicates existing heart problems and sometimes leads to a new diagnosis of heart failure.
Within two years of Actos’ release, Canadian health officials issued an advisory regarding an increasing number of heart failure, pulmonary edema and pleural effusion (fluid in the lungs) cases connected to the drug.
Heart Problems and TZDs
Actos, and its predecessor, Avandia (rosiglitazone), are both TZDs, which makes them structurally and mechanically similar. They work by making cells more receptive to insulin, a naturally occurring hormone produced by the pancreas.
The problems with TZDs date back to early 2000, when the first in this drug family, Rezulin (troglitazone), was taken off the market due to hepatic (liver) toxicity. In 2007, patients taking Avandia were shocked when a study found Avandia increased heart attack risk as much as 43 percent. Amid an outcry from physicians and watchdog groups, the U.S. Food and Drug Administration (FDA) added a black-box warning and severely limited access to the drug.
The Avandia scandal ran deep, with criticism over the FDA’s handling of the case and reports that drugmaker GlaxoSmithKline sought to intimidate doctors who criticized the drug. Today, up to 50,000 lawsuits have been settled, with thousands more pending.
FDA Warning About Actos and Heart Failure
Heart failure, sometimes called congestive heart failure (CHF), happens when the heart can’t supply an adequate blood flow to meet the body’s needs. When this happens, the body often becomes congested with fluids. Typically, heart failure presents itself when either side of the heart, or both sides, fail. When this happens, breathing becomes labored, edema (swelling) sets in and organs can start failing.
In the United States, it took several years before drug regulators took notice of Actos-related heart problems. A 2007 study that ran in the Journal of the American Medical Association (JAMA) noted that “serious heart failure is increased by pioglitazone, although without an associated increase in mortality.”
Another JAMA-published study that compared rosiglitazone and pioglitazone stated, “Both thiazolidinediones have been shown to increase the risk of heart failure compared with treatment with placebo or other anti-diabetes medications.”
In 2007, the FDA required Actos to carry a black-box warning regarding heart failure, stating that TZDs can cause or exacerbate heart failure in patients. The warning goes on to say Actos patients should be monitored closely for signs of heart failure and those who have heart failure should start Actos on a low dose or not use it at all.
Since the black-box warning was issued, other medical associations have also decided to take a closer look at Actos. In 2010, the American College of Cardiology and the American Heart Association issued a joint advisory, recommending that the use of TZDs should be closely monitored. It is recommended that diabetes patients taking Actos should speak with their doctors about the drug’s associated risks, especially those with active heart failure or anyone at elevated risk for the condition.
Actos and Heart Failure Lawsuits
It’s unclear exactly how many patients have died or suffered serious heart failure-related injuries after taking Actos. However, some court records offer a glimpse into Actos’ track record.
In a complaint filed in the U.S. District Court in Massachusetts, a former medical reviewer alleged that Takeda Pharmaceuticals hid the heart risks associated with the drug’s use. Helen Ge, M.D., claimed that Takeda failed to properly report hundreds of congestive heart failure cases to the FDA’s adverse event reporting system. Takeda, like all drugmakers, is required to update the database to provide the FDA with a better understanding of drug interactions.
Ge, who sued under the federal False Claims Act, said the company was motivated to fraudulently report and underreport adverse events to enhance Actos’ safety profile and increase sales. At the same time, patients have been coming forward with more heart failure complaints against Actos and Takeda. Ge's case has since been dismissed.
In one case, a Texas man whose wife died of heart failure after taking Actos filed a federal lawsuit against Takeda. The man said his wife started taking Actos in 2006 to treat her Type 2 diabetes. On June 20, 2011, she was diagnosed with congestive heart failure, which led to her death, her family said.