FDA adds warnings about heart failure risk to labels of type 2 diabetes medicines containing saxagliptin and alogliptin.

U.S. Food and Drug Administration (FDA) safety review has found that type 2 diabetes medicines containing saxagliptin and alogliptin may increase the risk of heart failure, particularly in patients who already have heart or kidney disease. Heart failure can result in the heart not being able to pump enough blood to meet the body’s needs.

Saxagliptin and alogliptin are part of the class of dipeptidyl peptidase-4 (DPP-4) inhibitor drugs, which are used with diet and exercise to lower blood sugar in adults with type 2 diabetes. Untreated, type 2 diabetes can lead to serious health problems, including blindness, nerve and kidney damage, and heart disease.In addition to heart failure, other possible side effects of saxagliptin and alogliptin include inflammation of the pancreas (pancreatitis), severe joint pain (arthralgia), allergic reactions, and low blood sugar (hypoglycemia) when combined with other prescription medicines used to treat diabetes

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.

Health care professionals should consider discontinuing the medicine 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.

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.

The Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR) trial was a large, prospective, multicenter, randomized, double-blind, placebo-controlled trial conducted in 16,492 patients with type 2 diabetes mellitus having established cardiovascular disease or at high risk of cardiovascular disease. Patients were followed for a median duration of 2 years and up to a total of approximately 2.8 years. More patients randomized to the saxagliptin group (289/8280, 3.5%) were hospitalized for heart failure compared to patients randomized to placebo (228/8212, 2.8%). In a time to first event analysis, the risk of hospitalization for heart failure was significantly higher in the saxagliptin treatment group (estimated hazard ratio: 1.27; 95% confidence interval: 1.07, 1.51). Identified risk factors in patients hospitalized for heart failure included a history of heart failure or renal impairment.

The Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care in Patients with Type 2 Diabetes Mellitus and Acute Coronary Syndrome (EXAMINE) trial was a multicenter, randomized, double-blind, placebo-controlled trial. It enrolled 5,380 patients with type 2 diabetes and established cardiovascular disease who had a recent acute coronary syndrome event (i.e., acute myocardial infarction or unstable angina requiring hospitalization). Patients were followed for 1.5 years on average and up to a total of 3.4 years. More patients randomized to the alogliptin group (106/2701, 3.9%) experienced at least one hospitalization for heart failure compared to patients randomized to placebo (89/2679, 3.3%).

As a result, FDA have added new Warnings and Precautions to the labels of medicines that contain saxagliptin or alogliptin to inform of the potential increased risk of heart failure.

Health care professionals and patients should report side effects involving saxagliptin, alogliptin, or other medicines to the FDA.



FDA’s Endocrinologic and Metabolic Drugs Advisory Committee meeting