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FDA to Review DPP-4 Inhibitor Saxagliptin for Increased Heart Failure Risk

SAVOR (Saxagliptin Assessment of Vascular Outcomes Recorded in patients with diabetes mellitus) trial showed a 27% increase in hospitalizations for heart failure among patients receiving saxagliptin as opposed to placebo….

Dipeptidyl peptidase-4 (DPP-4) inhibitors increase the concentration of active incretin hormones, stimulating the release of insulin and decreasing the levels of glucagon. DPP-4 inhibitors include sitagliptin, alogliptin, linagliptin and saxagliptin. Saxagliptin, branded as Onglyza, has been in the spotlight since ever since it was FDA approved. Saxagliptin showed remarkable glycemic control in type 2 diabetic patients with only minor adverse events.

Previous studies of saxagliptin and cardiovascular outcomes showed fluctuating results. Some studies did not show any increased or decreased risk for cardiovascular outcomes. Other studies showed that this particular DPP-4 inhibitor had some association with cardiovascular events when compared to placebo. A 2013 Bristol-Myers publication confirmed that saxagliptin does meet safety endpoints concerning cardiovascular death and non-fatal myocardial infarction and stroke when added to standard diabetic care.

In January of this year, The New England Journal of Medicine published a correspondence concerning saxagliptin as well as other DPP-4 inhibitors and their association with cardiovascular outcomes. The correspondence was to the Saxagliptin Assessment of Vascular Outcomes Recorded in patients with diabetes mellitus (SAVOR) trial. The SAVOR trial showed a 27% increase in hospitalization for heart failure among patients receiving saxagliptin as compared to patients receiving the placebo. Safety of these agents as it relates to cardiovascular health needs to be clarified and is now under FDA investigation; data from all DPP-4 inhibitor trials must be reported to the FDA by March 1. Studies have shown that substrates of the enzyme, DPP-4, have brain natriuretic peptides 100 times as high as patients with heart failure. Other trials have been evaluated but their prevalence may not be of much value due to 38% of the patients having heart failure prior to the use of saxagliptin.

In conclusion, this correspondence is to caution prescribers and patients of the possible cardiovascular risk associated with DPP-4 inhibitors use. The FDA advised patients to not stop taking saxagliptin until further evaluation is done or otherwise noted by prescribers.

This study correspondence does provoke interest in patients and prescribers administering saxagliptins to type 2 diabetic patients who may also have other cardiovascular risk factors.

Standl, Eberhard. Saxagliptin, Alogliptin, and Cardiovascular Outcomes. NEJM. 2014 Jan 30; 370:483-484.