Results from a multinational clinical trial found that while the antihyperglycemic drug saxagliptin met the FDA’s cardiovascular safety standards, it offered no cardiovascular protection and unexpectedly increased the risk of hospitalization for heart failure among diabetics at high risk for heart disease. These findings were presented Sept. 2 at the European Society of Cardiology Congress 2013 in Amsterdam and published in the New England Journal of Medicine.
The Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes-Thombolysis in Myocardial Infarction (SAVOR-TIMI) trial took place at 788 sites in 26 countries between May 2010 and Dec. 2011. The study sought to assess the safety and efficacy of the drug, a selective dipeptidyl peptidase 4 inhibitor, in cardiovascular outcomes in at-risk diabetic patients. AstraZeneca and Bristol-Myers Squibb paid for the research.
“With the possible exception of trials of metformin and insulin, most reported trials to date evaluating the effects on cardiovascular outcomes of specific glucose-lowering strategies or medications either have been insufficiently powered or have shown no significant cardiovascular benefit or an increased risk of death,” explained the authors, co-led by Benjamin M. Scirica, MD, MPH, and Deepak L. Bhatt, MD, MPH, of Brigham and Women’s Hospital in Boston.
SAVOR-TIMI randomly assigned more than 16,000 type 2 diabetic patients with a glycated hemoglobin level of 6.5 percent to 12 percent who were at risk for or had cardiovascular disease to receive saxagliptin (Onglyza, AstraZeneca and Bristol-Myers Squibb) or a placebo. Participants were followed for an average of 2.1 years.
The researchers utilized the combination of cardiovascular death, nonfatal MI or nonfatal ischemic stroke as the primary safety and efficacy outcome. As a secondary efficacy endpoint, they used the primary outcome plus hospitalization for heart failure, coronary revascularization or unstable angina.
Saxagliptin met the safety standard by neither reducing nor increasing the risk of the primary outcome when added to the standard care of diabetics at risk for cardiovascular disease. However, the drug did not offer any cardiovascular protection.
The primary endpoint occurred in 7.3 percent of the saxagliptin group and 7.2 percent of the placebo group. The secondary outcome occurred in 12.8 percent of the experimental group and 12.4 percent of the controls.
The drug also did not increase the risk of adverse outcomes, namely acute or chronic pancreatitis.
However, more saxagliptin patients were hospitalized for heart failure, a finding the researchers called “unexpected” and one that warrants additional study to confirm.
In combination with studies of other similar drugs, the authors wrote, “these data will provide a more rigorous and robust evidence base than is currently available to guide the future care of patients with diabetes.”