FDA Reviewing Saxagliptin Trial Data for Possible HF Risk


February 11, 2014

BETHESDA, MD – The US Food and Drug Administration is investigating a possible risk of heart failure among patients with type 2 diabetes treated with saxagliptin (Onglyza or Kombiglyze XR, Bristol-Myers Squibb/AstraZeneca)[1].

The agency issued a communication this morning stating it has requested clinical data from the manufacturer so that it can investigate the potential risks. In the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR-TIMI 53) trial, published in the New England Journal of Medicine and presented at the European Society of Cardiology 2013 Congress, saxagliptin was associated with a significant 27% increased risk of hospitalizations for heart failure, a component of the prespecified secondary end point.

"At this time, we consider information from the study to be preliminary," according to the FDA. "Our analysis of the saxagliptin clinical-trial data is part of a broader evaluation of all type 2 diabetes drug therapies and cardiovascular risk." The company is expected to submit all clinical-trial data to the FDA by the end of March. At that time, the FDA will begin an analysis of the data and report the findings publicly when it is completed.

In SAVOR-TIMI 53, saxagliptin failed to reduce the composite end point of cardiovascular death, nonfatal MI, or nonfatal ischemic stroke when added to usual care in patients with type 2 diabetes with either a history of established CVD or multiple CVD risk factors. Use of saxagliptin was not associated with an increased risk of other cardiovascular events, such as death, MI, or stroke.

Saxagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor approved in the US, Canada, Europe, and elsewhere as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. As reported previously, saxagliptin was the first new diabetes drug to receive FDA approval after the issuance of new agency guidelines that required companies to perform cardiovascular-outcomes studies with new diabetes drugs. The company launched SAVOR-TIMI 53 to comply with the FDA regulations.

The FDA drug safety communication asks healthcare professionals and patients to report side effects related to the use of saxagliptin to the FDA MedWatch program. It also urges patients to not stop taking saxagliptin but instead speak with their doctor if they have any questions or concerns. Physicians should continue to follow the prescribing recommendations in the drug labels.

Experts have varied in their advice regarding this issue. Some cardiologists have said DPP-4 inhibitors should not be given to those with heart failure, while others, including many diabetologists, say existing heart failure should not preclude the use of DPP-4 inhibitors—rather, physicians must just be vigilant regarding the possibility of an association, particularly during the first six months of therapy with the diabetes drugs, which seems to be the major danger period.


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