In light of evidence suggesting a possible link between the diabetes medication Onglyza and heart failure, an FDA panel has recommended amendments to the drug’s warning label.

The panel’s review was prompted by a study published in the New England Journal of Medicine that showed increased rates of hospitalization for heart failure in patients treating type-2 diabetes with Onglyza.

After FDA review, 14 of the 15 panelists voted to update the label for Onglyza with new safety information. One panelist voted to take Onglyza off the U.S. drug market.

The FDA panelists were primarily concerned that Onglyza might increase the risk of cardiovascular disease more than the FDA-imposed maximum of 30 percent. This includes conditions like cardiovascular death, nonfatal myocardial infarction, or nonfatal ischemic stroke.

After reviewing a study of over 16,000 type-2 diabetes patients known as the SAVOR-TIMI 53 trial, the panel was satisfied that Onglyza did not present an unacceptable risk of cardiovascular disease.

However, the panel noted that patients in the SAVOR study had a 27 percent increase in the rate of the first event of hospitalization for heart failure. Panelists commented that an increase that large seemed to be a “real signal” and that even if clinicians may be able to predict which patients are at higher risk for heart failure, a change in labeling is warranted. The current label for Onglyza does not mention heart failure.

Heart failure, distinct from cardiovascular disease, is a condition in which the heart does not move enough blood to meet the body’s demand. This condition can starve the body for needed nutrients and can also result in the buildup of excess fluid throughout the body, a condition known as congestive heart failure.

Symptoms of congestive heart failure include fatigue, dizziness, bloating, congestion in the lungs, excessive need to urinate, and a heart rate that is faster or more irregular than normal.

Onglyza Side Effects

Onglyza is the brand name used by manufacturer AstraZeneca for the drug saxagliptin. The same active ingredient is used in the drug Kombiglyze XR, which combines it with the drug metformin.

Onglyza was approved by the FDA in July 2009 as a treatment for high blood sugar in patients with type-2 diabetes, not those with type-1 diabetes.

Due in part to its ability to control blood sugar without stimulating weight gain, Onglyza has been particularly popular. Sales in 2012 exceeded $700 million, and by 2018 annual sales of Onglyza are predicted to exceed $2.4 billion.

The panel’s review grew out of an effort begun by the FDA in 2008 to investigate the risk of cardiovascular disease associated with certain diabetes medications. Manufacturers of diabetes medications are now asked to provide additional evidence that their products do not increase the risk of adverse cardiovascular events.

In implementing this policy, the federal agency noted that diabetes patients already have two to four times the normal risk of heart disease than persons without diabetes.

To ensure that diabetes medications are not increasing that already elevated risk, the FDA has since required stricter design and data collection requirements for certain clinical trials of these medications.