In 2016, the FDA issued an Onglyza FDA warning regarding the increased risk for heart failure in patients taking the type-2 diabetes drug.

Onglyza is AstraZeneca’s name brand for saxagliptin, a drug in the class of dipeptidyl peptidase-4 (DPP-4) inhibitors. A warning was added to the drug’s label because patients with cardiovascular or kidney disease are at an increased risk for heart failure while taking the medication.

The combination medication Kombiglyze XR by AstraZeneca also includes the warning because it is a mixture of saxagliptin and metformin.

Basis for Onglyza FDA Warning

The FDA was prompted to issue the warning after two studies were made public at the European Society of Cardiology’s 2013 meeting. The studies also were subsequently published in the New England Journal of Medicine.

The “Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus – Thrombolysis in Myocardial Infarction 53” (SAVOR-TIMI 53) clinical study included 16,492 patients who had type-2 diabetes and had been diagnosed with cardiovascular disease or were at a high risk to develop cardiovascular disease.

According to the SAVOR-TIMI 53 results, a 27 percent increased risk was seen in patients needing hospitalization for an initial heart failure event and a possibly increased risk for mortality overall. Among the issues that appeared to be risk factors for cardiovascular events were a previous history of heart failure or kidney problems.

The other study was called Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE), which looked at 5,380 patients. Alogliptin is the generic version of Nesina, a DPP-4 inhibitor made by Takeda that competes with Onglyza for market share.

The EXAMINE results found 3.9 percent of patients who received alogliptin required hospitalization for heart failure. A lesser total of 3.3 percent of patients who received a placebo (fake pill) instead were hospitalized for heart failure.

Researchers are unsure why the Onglyza patients experienced a higher risk of heart failure than the Nesina patients since both drugs are in the same class. However, the warning was placed on Nesina labels because the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee could not determine the mechanism that caused Onglyza to show a higher number of heart failure outcomes.

A majority of the committee members voted to add the warning to both drugs because they belong to the same class and work much the same way.

The Onglyza FDA warning also covers combination drugs, including Kombiglyze XR by AstraZeneca, which is a mixture of saxagliptin and metformin. Other DPP-4 inhibitor combination drugs covered by the warning include Kazano by Takeda, which contains alogliptin and metformin, and Oseni by Takeda, which is a mixture of alogliptin and pioglitazone.

Another study, the TECOS trial, indicated that Januvia (sitagliptin) by Merck was not associated with an increased risk of heart failure, despite sitagliptin also belonging to the DPP-4 inhibitor drug classification.

The TECOS study involved 14,671 patients with type-2 diabetes who took either sitagliptin or a placebo. Researchers reported the TECOS trial results at the American Diabetes Association 2015 Scientific Sessions.

What to Watch For

Medical professionals are also encouraged to submit reports of serious serious saxagliptin and alogliptin side effects to the FDA’s MedWatch program. The symptoms of heart failure include, but are not limited to:

• Shortness of Breath
• Fatigue
• Swelling in Legs, Ankles, and Feet
• Rapid or Irregular Heartbeat
• Persistent Cough or Wheezing with White or Pink Phlegm

Onglyza Heart Failure Prompts Legal Action

Although the issue needs more research, enough Onglyza patients have suffered from heart complications and have filed lawsuits to create an Onglyza MDL. Plaintiffs in several Onglyza lawsuits sought consolidation in 2018 so that their legal claims can be handled more efficiently without countless individual trials. The cases are now centered in Kentucky federal court.

According to Onglyza heart failure plaintiffs, drug manufacturers failed to properly warn patients and doctors about the risks for heart failure while taking Onglyza. If the plaintiffs and their doctors were warned of these risks, they would have allegedly chosen not to treat their diabetes with Onglyza.

The Onglyza Heart Failure MDL is In re: Onglyza (Saxagliptin) and Kombiglyze XR (Saxagliptin and Metformin) Products Liability Litigation, MDL No. 5:18-md-02809-KKC, in the U.S. District Court for the Eastern District of Kentucky.