Onglyza Side Effects Increase Risk of Death, FDA Reviewers Warn

Federal drug experts are warning that side effects of the diabetes drug Onglyza may increase the risk of serious health problems, including death. 

According to briefing materials (PDF) released by FDA reviewers on Friday, ahead of tomorrow’s meeting of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee Meeting, the agency suggests that there may be an increase in “all cause mortality” linked to Onglyza side effects, which could potentially affect the entire class of drugs.

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. However, only drugs with the active ingredient saxagliptin are being reviewed.

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.

According to the FDA reviewers, There was a 27% increased risk of heart failure hospitalization for patients given Onglyza. Researchers also at first found a slight, but insignificant-appearing increased risk of cardio-vascular (CV) and all-cause death. However, when they conducted a closer analysis, they found that the death risks were significant after all.

“Increases appeared across both CV and non-CV categories of deaths, and exploratory analyses to elucidate the etiology behind the all-cause mortality signal were unrevealing and did not shed light on a mechanism beyond treatment differences,” the reviewers noted. “We are convening this meeting of the Endocrinologic and Metabolic Drugs Advisory Committee to discuss the safety findings from SAVOR and seek advice and recommendations on these issues.”

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.

An advisory panel of outside experts will be convened tomorrow by the FDA, to discuss the results of the study and vote on any recommendations to the agency about whether regulatory actions are necessary to protect the public. While the advisory committee’s recommendations are not binding on the FDA, such findings often have a significant influence on any ultimate decisions about new warnings or other steps that may be necessary to protect the public.

Onglyza Pancreatic Cancer Concerns

Onglyza is a DPP-4 inhibitor, which is part of a class of drugs known as incretin mimetics, which 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.

In addition to the potential risk of heart failure, studies have suggested that users may face a risk of pancreatic cancer from Onglyza and other incretin mimetic diabetes drugs.

A number of Byetta lawsuits, Januvia Lawsuits, Janumet lawsuits and Victoza lawsuits are currently pending in courts throughout the country involving similar incretin mimetic diabetes drugs, alleging that the makers of those medications failed to adequately warn about the risk that users may develop pancreatic cancer.

The incretin mimetic litigation pending throughout the federal court system has been consolidated as part of an MDL, or Multidistrict Litigation, which is centralized before U.S. District Judge Anthony J. Battalglia in the Southern District of California to reduce duplicative discover, avoid conflicting pretrial rulings from different judges and to serve the convenience of the parties, witnesses and the courts.