Rationale, design, and baseline characteristics in Evaluation of LIXisenatide in Acute Coronary Syndrome, a long-term cardiovascular end point trial of lixisenatide versus placebo

Am Heart J. 2015 May;169(5):631-638.e7. doi: 10.1016/j.ahj.2015.02.002. Epub 2015 Feb 12.


Background: Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Furthermore, patients with T2DM and acute coronary syndrome (ACS) have a particularly high risk of CV events. The glucagon-like peptide 1 receptor agonist, lixisenatide, improves glycemia, but its effects on CV events have not been thoroughly evaluated.

Methods: ELIXA (www.clinicaltrials.gov no. NCT01147250) is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study of lixisenatide in patients with T2DM and a recent ACS event. The primary aim is to evaluate the effects of lixisenatide on CV morbidity and mortality in a population at high CV risk. The primary efficacy end point is a composite of time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. Data are systematically collected for safety outcomes, including hypoglycemia, pancreatitis, and malignancy.

Results: Enrollment began in July 2010 and ended in August 2013; 6,068 patients from 49 countries were randomized. Of these, 69% are men and 75% are white; at baseline, the mean ± SD age was 60.3 ± 9.7 years, body mass index was 30.2 ± 5.7 kg/m(2), and duration of T2DM was 9.3 ± 8.2 years. The qualifying ACS was a myocardial infarction in 83% and unstable angina in 17%. The study will continue until the positive adjudication of the protocol-specified number of primary CV events.

Conclusion: ELIXA will be the first trial to report the safety and efficacy of a glucagon-like peptide 1 receptor agonist in people with T2DM and high CV event risk.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / drug therapy*
  • Aged
  • Cardiovascular Diseases
  • Double-Blind Method
  • Female
  • Glucagon-Like Peptide 1 / agonists
  • Humans
  • Male
  • Middle Aged
  • Peptides / pharmacology
  • Peptides / therapeutic use*
  • Placebos
  • Protein Kinase Inhibitors / therapeutic use*
  • Research Design
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Peptides
  • Placebos
  • Protein Kinase Inhibitors
  • lixisenatide
  • Glucagon-Like Peptide 1
  • p38 Mitogen-Activated Protein Kinases

Associated data

  • ClinicalTrials.gov/NCT01147250