The FDA has warned diabetes patients with signs of heart problems to be aware that their risk of heart failure could increase if they take Onglyza (saxagliptin).

Onglyza belongs to a class of drugs called dipeptidyl peptidase-4 (DPP-4) inhibitors. AstraZeneca’s Onglyza and similar drugs in this class work to control diabetes by stimulating the pancreas to produce insulin.

The very first DPP-4 inhibitor was Avandia, which was recalled after it was associated with an increased risk of heart-related death.

Onglyza and Signs of Heart Problems

Under the heading Important Safety Information, Onglyza’s label warns patients to tell their doctors if they have ever had heart failure or kidney problems.  The medication’s warnings list signs of heart failure that include:

• Shortness of breath or trouble breathing, especially upon laying down
• Unusually quick weight increase
• Swelling or fluid retention, often seen in the feet, ankles or legs
• Unusual fatigue

The FDA became aware that patients with a history of cardiovascular or kidney disease were at an increased risk for heart failure after two different studies were made public in 2013.

The Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus – Thrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) clinical study looked at 16,492 patients who had type-2 diabetes and had either already suffered a stroke or heart attack or had a high risk of developing cardiovascular disease. The average age of the patients was 65 years old. The study found that Onglyza users faced heart risks. 

The SAVOR-TIMI 53 results were presented at the European Society of Cardiology’s 2013 annual meeting where researchers disclosed that Onglyza patients had a 27 percent increased risk of needing hospitalization for an initial heart failure event and a possible increased risk for death overall.  The most important risk factors were a previous history of heart failure or kidney issues.

The second study, the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE), included 5,380 patients. Alogliptin is the generic version of Nesina, a DPP-4 inhibitor from Takeda which is a competitor of Ongylza. The EXAMINE study surprised researchers because a total of 3.9 percent of patients on alogliptin needed hospitalization for heart failure compared to 3.3 percent who received a placebo instead. Those figures are very close.

Because both alogliptin (Nesina) and saxagliptin (Onglyza) are in the same drug class of DPP-4 inhibitors, researchers assumed they would see similar increases of heart failure among alogliptin users, but they did not.

Despite the EXAMINE study’s results, the FDA decided the warning of an increased risk of heart failure should go on the labels of both medications because they work so similarly.

The FDA’s warning includes Onglyza combination drugs. Those include Kombiglyze XR by AstraZeneca, which is a mixture of saxagliptin and metformin. Other DPP-4 inhibitor combination drugs covered by the increased risk of heart failure warning include Kazano by Takeda, which contains alogliptin and metformin, and Oseni by Takeda, which is a mixture of alogliptin and pioglitazone.

Patients taking any of these DPP-4 inhibitors or combination drugs should learn to recognize signs of heart problems.