Citing safety concerns, pharmacy benefits manager Express Scripts has announced it has removed the diabetes medication Onglyza from its National Preferred Formulary.

The provider released its 2016 formulary in July 2015, including a list of medications it will no longer provide coverage for.

A representative for Express Scripts says the company excluded Onglyza because of concerns about the increased risk of hospitalization for heart failure associated with that drug. The representative noted that Onglyza’s competitor Januvia showed no such risk.

In April 2013, an FDA advisory committee concluded that the label for Onglyza should include a warning alerting doctors and patients to the higher incidence of hospitalization for heart failure found in association with Onglyza.

The FDA committee cited a study that found Onglyza patients had a 27 percent higher risk of heart disease than subjects who took a placebo.

That and one other study of saxagliptin (the generic name for Onglyza) were the first two trials to be completed in response to a 2008 guidance issued by the FDA, which required manufacturers of medications for type-2 diabetes to verify that those medications did not create an unacceptable risk of cardiovascular complications.

Despite the study findings, the committee deemed the risk acceptable, as it fell below the 30 percent limit set in the 2008 guidance. One member of the FDA panel recommended withdrawing the drug from the U.S. market.

The studies also showed a higher rate of death for Onglyza patients as compared to those who took a placebo. The committee did not consider this finding significant, however, since there was no apparent reason for the higher rates of death.

Onglyza was first approved by the FDA in 2009 as a treatment for type-2 diabetes. In 2014, Onglyza sales reached $820 million.

Onglyza is one of a relatively new group of diabetes medications called incretin mimetics. Other drugs in the same class include Byetta, Janumet, Januvia, Nesina and Victoza.

These medications work by imitating the action of incretin hormones, the hormones that the body releases after eating that stimulate the release of insulin.

Its action is complementary to that of the older diabetes medication metformin, which works by reducing glucose production by the liver, decreases absorption of glucose in the intestines, and helps cells absorb glucose out of the bloodstream.

Both metformin and saxagliptin, the active ingredient in Onglyza, are combined in a formulation brand-named Kombiglyze XR, which like Onglyza is manufactured by the London-based drug maker AstraZeneca. Express Scripts has also discontinued coverage for Kombiglyze XR due to the same safety concerns related to saxagliptin.

According to Express Scripts’s announcement, the company’s formulary provides prescription drug coverage for 25 million people in the United States, making it the most widely used formulary.

The company says that for Onglyza and each of the other 79 drugs excluded from the formulary, there exists a clinically equivalent alternative medication that’s available at a lower cost.

Express Scripts says the exclusion will result in fewer than 0.5 percent of its National Preferred Formulary members being asked to use a different medication.