American Diabetes Association (ADA) 75th Scientific Sessions 2015:

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

The first clinical trial to examine cardiovascular safety in a glucagon-like peptide 1 (GLP-1) receptor agonist in patients with diabetes has found a neutral effect on heart failure and other cardiovascular outcomes.

Marc Pfeffer, MD, PhD, Dzau Professor of Medicine at Harvard Medical School and Senior Physician in Cardiology at Brigham and Women’s Hospital, was the Principal Investigator for the Evaluation of LIXisenatide in Acute coronary syndrome (ELIXA) trial. Dr. Pfeffer presented results of ELIXA at the American Diabetes Association’s 75th Scientific Sessions, in Boston, from June 5–9.


GLP-1 Receptor Agonists Have Been Used Under a Cloud of Suspicion
GLP-1 receptor agonists may be used as secondary therapy when other agents 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,” Dr. Pfeffer said. “There has also been some hope that some of these drugs may improve cardiovascular health.”

Dr. Pfeffer continued, “GLP-1 receptor agonists were being used around the world while cardiovascular safety had yet to be established. ELIXA was the first clinical trial to assess cardiovascular outcomes in this class of drugs. We have shown that patients and their healthcare providers have no cause for concern with this class, even if patients are at high risk for heart-related problems.”

Over 6000 Patients Were Studied
Specifically, the ELIXA study found no increased risk for cardiovascular death, heart attack, stroke, unstable angina, or heart failure in people with type 2 diabetes who had recently experienced acute coronary syndrome. The study examined 6068 people from 49 countries, who were randomly assigned to lixisenatide or placebo, with a follow-up period of more than 2 years.

No Increased Hypoglycemia Risk Was Observed
The ELIXA trial also showed that those who took lixisenatide were no more likely to experience hypoglycemia 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 the Cardiovascular Division at Brigham and Women’s Hospital. Dr. Lewis continued, “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 in doing so, we don’t want to add any additional risks.”

Lixisenatide Conferred Other Benefits As Well
Dr. Pfeffer added that ELIXA also found a modest benefit for weight control, and no increase of risk for hypoglycemia or pancreatic injury in patients who took lixisenatide.

“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.

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

Patients and their healthcare providers have no cause for concern regarding cardiovascular safety with the GLP-1 class, even when patients are at high risk for cardiovascular disease.

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