Hospitalization Risk from Onglyza Heart Failure Questioned in New Study

Although an FDA advisory panel recently called for stronger warnings about potential Onglyza heart failure risks, the manufacturer of the diabetes drug has presented data that appears to question whether there is a link.

At a meeting of the American Diabetes Association (ADA) in June, research was presented by AstraZeneca that found no evidence that users face an increased risk of hospitalization from heart failure while using Onglyza. The review of data from an observational, retrospective insurance claims database study has not yet been published for peer review.

Onglyza (saxagliptin) was developed jointly by AstraZeneca and Bristol-Myers Squibb, but is now owned wholly by AstraZeneca. It was approved by the FDA in July 2009, for treatment of type 2 diabetes, and the medication is part of a class of drugs known as incretin mimetics, which also includes Januvia, Janumet, Byetta, Victoza and other widely used medications.

In April, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted 14-1 to recommend stronger warnings about the potential Onglyza heart risks, after a review of data from clinical trials suggested that users may face a higher than expected risk of hospitalization for heart failure and all-cause mortality.

At issue is data collected from a clinical trial known as SAVOR, which involved 16,492 subjects with type 2 diabetes, some of whom were given Onglyza, and some of whom were given a placebo.

AstraZeneca indicated in a recent press release that the new analysis used real world data from an insurance claims database to compare Ongylza use with those that use the diabetes drug Januvia, and a class of drugs known as sulfonylureas, such as metformin, Micronase and DiaBeta. Researchers found that Onglyza and Januvia had lower risks of hospitalization for heart failure than those given sulfonylureas, and could find no increased risk of heart failure when comparing Onglyza and Januvia to slufonylureas, or when comparing Onglyza to Januvia.

FDA reviewers previously indicated that the SAVOR results suggested that there may be a 27% increased risk of heart failure hospitalization on Onglyza. They also found both increases in cardiovascular death and death from all causes.

The FDA’s advisory committee had several possible options, including new label warnings, limiting Onglyza’s availability, or recommending an Onglyza recall. In the end, only one committee member voted for a recall. The other 14 called for new label warnings. While the agency has not yet acted on the recommendations, the FDA usually follows the guidance of their advisory committees.

Onglyza is a DPP-4 inhibitor, which is part of a class of drugs known as incretin mimetics that works by mimicking the incretin hormones the body usually produces to naturally stimulate the release of insulin in response to a meal. The diabetes drug brought in more than $700 million in sales in 2012. Other DPP-4 inhibitors include Nesina and Januvia.

The FDA launched an investigation into the potential heart risks with Onglyza last year, following the publication of the SAVOR study by the New England Journal of Medicine in 2013.