Lyxumia trial shows neutral CV risk in adults with type 2 diabetes, high risk for CVD

Issue: July 2015

BOSTON — The GLP-1 receptor agonist Lyxumia lowers HbA1c without any cardiovascular risk or benefit in adults with type 2 diabetes at high risk for acute cardiovascular events, according to study findings presented here.

In announcing results from the ELIXA cardiovascular outcomes study, a worldwide randomized, double blind, placebo-controlled trial, researchers also found no increased risk for hypoglycemia or pancreatic injury among participants assigned Lyxumia (lixisenatide, Sanofi), as well as a modest benefit on weight after 3 years of treatment.

“In these high risk patients, we’re safe from a cardiovascular point of view, favorable on some metabolic points of view,” Marc Pfeffer, MD, PhD, of Harvard Medical School and Brigham and Women’s Hospital, said in a press conference announcing the results of the study. “This should provide physicians and patients reassurance for this adjunctive therapy to better control their glucose status.”

Pfeffer, one of the investigators for the ELIXA trial, Rhonda M. Bentley-Lewis, MD, MBA, of Massachusetts General Hospital, and colleagues at other institutions analyzed data from 6,068 adults from 49 countries with type 2 diabetes, an HbA1c of 7.5% and acute post-coronary syndrome within 180 days of randomization (mean age, 60 years; 30% female, 76% white; mean BMI 30). Within the cohort, 3,034 participants were assigned an initial dose of 10 mcg once daily of lixisenatide; the dosage was then increased to 20 mcg once per day. Site investigators were permitted to adjust the dose as needed up to the maximum of 20 mcg per day during the study period. The remaining participants (n = 3,034) were assigned a matching placebo.

Participants in both arms had a mean diabetes duration of 9 years, a mean fasting glucose of 149 and an mean HbA1c of 7.7%.

Matthew Riddle

Prior to their index acute coronary event, 22% of participants in both groups experienced myocardial infarction. Prior to randomization, 22% of participants in both groups experienced heart failure. The mean time period between acute coronary syndrome and randomization was 72 days.

Following a 3-year study period, cardiovascular outcomes were similar in the two treatment arms, with a hazard ratio of 1.02 for CV death, MI, stroke or angina; a hazard ratio of 0.96 for hospitalization due to heart failure and a hazard ratio of 0.94 for all-cause death.

Participants assigned lixisenatide saw a modest reduction in HbA1c over 3 years vs. participants assigned placebo (mean post-baseline difference, -0.27%), a mean weight decrease of .7 kg and an .8 mm Hg decrease in blood pressure.

The weight loss and blood pressure numbers “are small, but with big numbers [of participants] in the study, statistically significant and perhaps clinically significant,” Matthew Riddle, MD, of Oregon Health & Science University, said during the press conference.

Heart rate was not affected, according to researchers.

Adverse effects seen in similar studies, including nausea and vomiting, were increased in the lixisenatide group, leading to discontinuation of the drug in just under 5% of participating patients, Pfeffer said.

Researchers found no increase in pancreatitis or pancreatic cancer among participants, as well as no increase in incidents of severe hypoglycemia. – by Regina Schaffer

Reference:

Bentley-Lewis R, et al. Rationale, design and baseline characteristics in evaluation of lixisenatide in acute coronary syndrome, a long-term cardiovascular endpoint trial of lixisenatide vs. placebo. Presented at: American Diabetes Association’s 75th Scientific Sessions; June 5-9, 2015; Boston.

Disclosure: Pfeffer reports no relevant financial disclosures. Endocrine Today was unable to confirm any relevant financial disclosures for Bentley-Lewis and Riddle.