FDA Investigates Heart Failure Risk of Saxagliptin
The U.S. Food and Drug Administration (FDA) announced that it will evaluate clinical trial data from the manufacturer of saxagliptin (Onglyza and Kombiglyze XR) to investigate whether this medication is linked to an increased risk of heart failure.
The FDA investigation was initiated after publication of the results from the SAVOR-TIMI 53 trial in the New England Journal of Medicine in October. This randomized study involved 16,492 patients with type 2 diabetes who had a history of, or were at risk for, cardiovascular events and were randomized to saxagliptin or placebo for a median of 2.1 years. While saxagliptin was not linked to an increased risk for the composite primary end point of cardiovascular death, myocardial infarction, or ischemic stroke, significantly more patients treated with saxagliptin were hospitalized for heart failure (3.5% vs. 2.8%; hazard ratio, 1.27; P=0.007).
The FDA considers the results of the SAVOR-TIMI 53 trial to be preliminary and stated that the FDA’s investigation is part of a larger evaluation of the cardiovascular risk of medications used to treat type 2 diabetes. Furthermore, the FDA advised health care professionals to continue following prescribing recommendations found in the label for saxagliptin and that patients not stop taking this agent.
Putting the Risk Into Context
“It is important to put this risk into context, as the absolute risk excess of hospitalization for heart failure was 0.7% over 2 years. The average physician, and even a physician with a busy diabetes practice, probably wouldn’t detect that. It is only because we did a mega trial that we found this difference,” said co-principal investigator of the SAVOR-TIMI 53 trial Deepak L. Bhatt, MD, MPH, Professor of Medicine at Harvard Medical School, and Executive Director of Interventional Cardiovascular Programs at Brigham and Women’s Hospital.
He suggested that this excess risk may be a drug-specific side effect or, more likely, a class specific effect. “When trials of other DPP-4 inhibitors are done, assuming they examine heart failure and have adequate statistical power, we may see that DPP-4 inhibitors slightly raise the risk of hospitalization for heart failure,” Dr. Bhatt said. Another possibility is that intense glycemic control may cause heart failure in susceptible patients as this increased risk has also been found in studies of thiazolidinediones, he said. “Only further trials of DPP-4 inhibitors and related diabetes drugs will definitively settle the question of heart failure risk,” he added.