First CVD Outcome Trial of a GLP-1 Agonist Finds No Cardiac Risk or Benefit

Boston, Massachusetts
June 8, 2015

Popular Glucose-Lowering Drugs Also Show No Risk of Hypoglycemia or Pancreatic Injury, and Modest Benefit for Weight Compared to Placebo

One member of a widely prescribed class of drugs used to lower blood glucose levels in people with diabetes has a neutral effect on heart failure and other cardiovascular problems, according to the first clinical trial to examine cardiovascular safety in a GLP-1 receptor agonist, presented at the American Diabetes Association's 75th Scientific Sessions.

The Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA) study also found a modest benefit for weight control, and no increase of risk for hypoglycemia or pancreatic injury in those who took lixisenatide, one of several GLP-1 receptor agonists being prescribed around the world to treat people with type 2 diabetes. GLP-1 receptor agonists are derived from gut hormones and may be used as a secondary therapy when other medications fail to sufficiently lower blood glucose levels.

"There has been a cloud of suspicion over all new diabetes drugs, including GLP-1 agonists, over whether they may increase the risk for cardiovascular problems," said Marc Pfeffer, MD, PhD, Dzau Professor of Medicine at Harvard Medical, Senior Physician in Cardiology at Brigham and Women's Hospital and Principal Investigator for the ELIXA trial. "There has also been some hope that some of these drugs may improve cardiovascular health. GLP-1 receptor agonists were being used around the world while CVD safety had yet to be established. This is the first report of a clinical trial designed to assess cardiovascular outcomes in this class of drugs and we have shown that patients and their healthcare providers should have no cause for concern, even if they are at high risk for heart-related problems."

Specifically, the ELIXA study found no increased risk for cardiovascular death, heart attack, stroke, unstable angina (chest pain) or heart failure in people with type 2 diabetes who had recently experienced acute coronary syndrome events (an umbrella term referring to when blood supplied to the heart muscle is suddenly blocked) and were therefore at high risk for additional heart problems. The study examined 6,068 people from 49 countries, randomly assigning them to lixisenatide or placebo, with a follow-up period of more than two years.

Heart disease and stroke are the number one causes of death and disability among people with type 2 diabetes, who are two to four times more likely than those who do not have diabetes to suffer from these conditions. Because of this, the U.S. Food and Drug Administration has recently augmented cardiovascular surveillance for new drugs prescribed to treat elevated blood glucose in patients with type 2 diabetes, including GLP-1 receptor agonists.

The ELIXA trial also showed that those who took lixisenatide were not more likely to have problems with hypoglycemia (low blood glucose) than those who took placebo, despite better blood glucose control.

"Knowing these drugs can be prescribed safely gives physicians another tool to further lower glucose without producing more hypoglycemia, a potential complication of improved glycemic control," said Eldrin Lewis, MD MPH, Associate Professor of Medicine, Harvard Medical School, Advanced Heart Disease section of Cardiovascular Division at Brigham and Women's Hospital. "These drugs can provide a very important adjunct to therapy. We want to get people to target to minimize the future consequences of diabetes, but we don't want to add any additional risks in doing so."

The ELIXA trial also found no increase in pancreatitis or cancers and a modest benefit in terms of weight gain, said Matthew Riddle, MD, Professor of Medicine, in the Division of Endocrinology, Diabetes, & Clinical Nutrition, at Oregon Health & Science University. Those taking lixisenatide did not gain weight, while those taking placebo did.

Those taking lixisenatide did, however, report a higher number of episodes of nausea and vomiting, common side effects for GLP-1 receptor agonists. "Nausea and vomiting sometimes caused patients to discontinue the medication," said Riddle, "but in terms of serious reactions or pancreatic problems, there was no difference between the two groups and no increased risk."

Dr. Pfeffer will lead a symposium on The Evaluation of Lixisenatide in Acute Coronary Syndrome – The Results of ELIXA on Monday, June 8 from 2:15 – 4:15 p.m. The ELIXA results will be followed by results from another cardiovascular safety trial, Results from the Trial to Evaluate Cardiovascular Outcomes after Treatment with Sitagliptin (TECOS) from 4:30 – 6:30 p.m.

About the American Diabetes Association

Nearly half of American adults have diabetes or prediabetes; more than 30 million adults and children have diabetes; and every 21 seconds, another individual is diagnosed with diabetes in the U.S. Founded in 1940, the American Diabetes Association (ADA) is the nation’s leading voluntary health organization whose mission is to prevent and cure diabetes, and to improve the lives of all people affected by diabetes. The ADA drives discovery by funding research to treat, manage and prevent all types of diabetes, as well as to search for cures; raises voice to the urgency of the diabetes epidemic; and works to safeguard policies and programs that protect people with diabetes. In addition, the ADA supports people living with diabetes, those at risk of developing diabetes, and the health care professionals who serve them through information and programs that can improve health outcomes and quality of life. For more information, please call the ADA at 1-800-DIABETES (1-800-342-2383) or visit diabetes.org. Information from both of these sources is available in English and Spanish. Find us on Facebook (American Diabetes Association), Twitter (@AmDiabetesAssn) and Instagram (@AmDiabetesAssn)