On April 04, 1016, the FDA issued an updated and extended Drug Safety Communication which further substantiates the risk of heart failure with diabetes medications containing not only the active ingredient saxagliptin, but also the active ingredient alogliptin. Thus, the present FDA safety review has found that type 2 diabetes medicines containing either saxagliptin or alogliptin increase the risk of heart failure, particularly in patients who already have heart or kidney disease. Pharmacologically saxagliptin and alogliptin belong to the class of dipeptidyl peptidase-4 (DPP-4) inhibitors, which are used with diet and exercise to lower blood sugar in adults with type 2 diabetes.
FDA evaluated two large clinical trials conducted in patients with heart disease. These clinical trials were also discussed at the FDA Endocrinologic and Metabolic Drugs Advisory Committee meeting in April 2015. Each trial showed that more patients who received saxagliptin- or alogliptin-containing
medicines were hospitalized for heart failure compared to patients who received an inactive treatment called a placebo (see Data Summary in the FDA Drug Safety Communication for additional information). In the saxagliptin trial, 3.5% of patients who received the drug were hospitalized for heart failure versus 2.8% of patients who received a placebo. This is the same as 35 out of every 1,000 patients compared to 28 out of every 1,000 patients. Risk factors included a history of heart failure or kidney impairment. In the alogliptin trial, 3.9% of alogliptin-treated patients were hospitalized for heart failure versus 3.3% in the placebo group. This is the same as 39 out of every 1,000 patients compared to 33 out of every 1,000 patients.
According to FDA, health care professionals should consider discontinuing medications containing saxagliptin and alogliptin in patients who develop heart failure and monitor their diabetes control. If a patient’s blood sugar level is not well-controlled with their current treatment, other diabetes medicines may be required.
Patients taking these medicines should contact their health care professionals right away if they develop signs and symptoms of heart failure such as:
- Unusual shortness of breath during daily activities
- Trouble breathing when lying down
- Tiredness, weakness, or fatigue
- Weight gain with swelling in the ankles, feet, legs, or stomach
Patients should not stop taking their medicine without first talking to their health care professionals. Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program, online at www.fda.gov/MedWatch/report, by downloading the form, or by calling 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178
As a result of the performed risk analysis, FDA is adding new warnings about this safety issue to the drug labels of the affected products, i.e., Saxagliptin (Onglyza), Saxagliptin/Metformin (Kombiglyze XR), Alogliptin (Nesina), Alogliptin/Metformin (Kazano), and Alogliptin/Pioglitazone (Oseni).