A fresh stream of data is raising some concerns about a new class of diabetes medicines and their relation to long-term heart health.
The Food and Drug Administration's endocrinologic and metabolic advisory committee is reviewing studies of two DPP-IV inhibitors, the second largest class of diabetes drugs as measured in sales, and some of the evidence is troubling.
A post-market, 16,000 patient study of AstraZeneca's Onglyza, which was approved as saxagliptin in 2009, has found a correlation with heart failure hospitalizations. While the study did not find an increase in ischemic events like stroke or heart attack, diabetic patients taking the drug had an 27 percent higher risk of hospitalization for heart failure, along with a small but significant increase in all-cause mortality.
"There is a public health implication of this finding," the committee wrote in a pre-meeting document. "A substantial number of subjects with hospitalization for heart failure events, regardless of treatment assignment, had recurrent events and/or died during the trial. A safety signal for heart failure was not previously observed in the saxagliptin clinical program. Hospitalization for heart failure was neither a primary nor secondary trial endpoint, and there is the potential for false positive results due to multiple testing. However, the validity of this finding is supported by the large number of events reported in this trial, and the fact that hospitalization for heart failure was based on a pre-specified definition, and clinically adjudicated by an independent, blinded committee of specialists."
The FDA committee also reviewed data on a similar DPP-IV drug, Takeda's Nesina, approved in 2013, and did not find similar concerns about heart failure correlations. The first time incidents of cardiac death, heart attack or non-fatal stroke for those taking Nesina was about the same as those who had a placebo.
But the FDA is still keeping an eye out for risks associated with the class of DPP-IV inhibitors, which help diabetics enhance a natural hormone, GLP-1, to improve insulin secretion and reduce glucose production.
In 2008, the FDA issued guidance to require drug companies to conduct more studies to prove that the class of medicines do not come with increased cardiovascular risks.
The SAVOR trial of AstraZeneca's Onglyza was aimed at proving the drug could prevent heart attacks, strokes and other cardiovascular events that are more likely to plague diabetes patients. Patients in the trial had a history of heart disease or multiple risk factors, but those who took the drug with standard therapy didn't end up with any better or worse outcomes than those who took placebos.
AstraZeneca brought in about $820 million on Onglyza last year. Later this spring, the most popular DPP-IV inhibitor drug will be scrutinized by the FDA, Merck's Januvia, which accounted for $4 billion in sales last year. The goal of the agency is to see if the whole class of DPP-IV inhibitors are potentially coming with an increased risk of cardiovascular events.
Diabetes medications were the only non-specialty therapy class with a significant increase in spending 2014--up 18 percent to $97 per-member, per-year and likely to keeping rising at that rate thanks to newly approved sodium-glucose co-transporter 2 inhibitors.
Amid all the new diabetes treatments, though, there is uncertainty about their long-term benefit in curbing cardiovascular disease, the ultimate cause of death for some 65 percent of diabetics.