Safety Concerns Persist With Newer Type 2 Diabetes Drugs
Newer type 2 diabetes therapies continue to yield mixed safety reports.
Along with concerns about pancreatitis and pancreatic cancer, a sub-class of incretin-based pills called DPP-4 drugs such as Onglyza and Januvia are now linked to a slight increased risk of heart failure.
Critics of these drugs claim the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have been slow to respond to concerns and downplay the importance of data linking these drugs to inflammation of the pancreas and pancreatic cancer.
In addition, Roche halted development of its new diabetes drug, aleglitazar, which is in the same class as Avandia, over heart-related safety concerns.
Doctors Concerned About Increase in Heart Failure Risk
According to a recent study conducted by Brigham and Women's Hospital in Boston, AstraZeneca and Bristol-Myers Squibb's DPP-4 type 2 diabetes drug Onglyza and Takeda's Nesina increase the risk of heart failure.
"It is a little bit concerning," Dr. Christopher Grainger of Duke University Medical Center, who was not involved in the research, told Reuters. "I'm sure the FDA will want to know more about it."
The DPP-4 class of medications also includes Januvia and Janumet and works by blocking DPP-4, a protein that breaks down incretin. Incretin is a hormone that stimulates the pancreas to make insulin. By breaking down DPP-4, these drugs allow incretin to keep stimulating the pancreas to make more insulin in people with type 2 diabetes.
The Brigham study did show that the drugs do not increase the risk for heart attack, but they don't lower it either, as researchers had hoped.
Researchers presented the results of the two-year study of almost 16,500 patients who took Onglyza and the results of a separate study of 5,380 patients who took Nesina. One of the principal investigators in the Onglyza study, Dr. Deepak Bhatt, said the risk of heart failure was likely to be an issue with all DPP-4 drugs.
AstraZeneca says this "small" increase in the risk for heart failure does not change the risk profile for Onglyza, which had sales of $709 million in 2012. Januvia is the DPP-4 market leader, with annual sales of $5 billion, and Merck plans a similar study with results expected in 2014.
Concerns of Pancreatitis, Cancer Still Exist
These new heart failure concerns add to results from several studies that DPP-4 drugs and similar GLP-1 therapies (both referred to as incretin-based therapies) like Byetta and Victoza cause inflammation of the pancreas and pancreatic and thyroid cancer.
According to a report by investigators at the British Medical Journal (BMJ), drug regulators in both the United States and Europe have not responded quickly enough to these safety concerns.
Johns Hopkins University reported that people who take both Januvia and Byetta are twice as likely to be hospitalized for pancreatitis as those who take other types of type 2 diabetes drugs.
Also, a University of California, Los Angeles (UCLA) study found precancerous tissues in the pancreases of people who took incretin therapies and died of unrelated causes.
A number of people who took these drugs filed lawsuits against the drugs' makers after being diagnosed with pancreatic cancer.
While the FDA and the EMA both claim the current data available does not definitely link these drugs to cancer or pancreatitis, both agencies concede that more studies are needed.
'Safety Signals and Lack of Efficacy' Halt Drug's Development
Drugmaker Roche announced in August 2013 that it is stopping the development of its new type 2 diabetes drug, aleglitazar.
The drug is in the same class of medicines as the problematic Avandia, known for its risk of heart problems.
“I think it shows that the class of drugs has significant problems with toxicity, particularly cardiovascular toxicity," Dr. Steven E. Nissen, the chairman of cardiovascular medicine at the Cleveland Clinic told Zolmax News.
The drug was in the middle of a large-scale clinical trial when an independent safety monitoring committee recommended stopping it because of "safety signals and lack of efficacy." A company spokesman reported that participants in the trial suffered from heart failure, kidney problems and fractures.
Both aleglitazar and Avandia work by making type 2 diabetes patients more sensitive to insulin. However, Avandia was banned in Europe and restricted in the United States in 2010 after evidence linked it to an increased risk of heart attack.
Another drug in the same class, Actos, is also known for an increased risk of heart failure, along with links to bladder cancer.
Dr. A. Michael Lincoff, chairman of the study and chairman of cardiology at the Cleveland Clinic, maintains that aleglitazar did not raise or lower the risk of heart attacks, death or stroke when compared with placebo.
A number of companies have abandoned development of similar drugs due to safety concerns.