Adding lixisenatide to usual care failed to prevent major cardiovascular events in an industry-sponsored clinical trial involving patients with type 2 diabetes who had a recent acute coronary syndrome, according to a report published online Dec. 3 in the New England Journal of Medicine.
Lixisenatide, a GLP-1-receptor agonist, is a glucose-lowering agent that inhibits glucagon secretion, prompts insulin production in response to hyperglycemia, and slows gastric emptying. In preliminary studies, lixisenatide showed some cardioprotective effects in myocardial ischemia and heart failure. To assess whether the drug would benefit diabetes patients at high CV risk, investigators conducted a randomized double-blind trial comparing lixisenatide with placebo in 6,068 patients who had type 2 diabetes and who had experienced acute coronary syndrome (ACS) during the preceding 6 months.
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In addition to receiving usual diabetes care provided by their treating physicians, these patients (mean age, 60 years) were randomly assigned to self-administer once-daily subcutaneous injections of lixisenatide (n = 3,034) or a matching placebo (n = 3,034) and were followed for a mean of 25 months at 49 medical centers worldwide, said Dr. Marc A. Pfeffer of the cardiovascular division, Brigham and Women’s Hospital, and Dzau Professor of Medicine a Harvard Medical School, Boston.
The primary endpoint of the study – a composite of death from CV causes, nonfatal MI, nonfatal stroke, or hospitalization for unstable angina – occurred in 13.4% of patients receiving lixisenatide and 13.2% of those receiving placebo, a nonsignificant difference. There were no differences between the two study groups in any of the individual components of this composite endpoint (N Engl J Med. 2015 Dec. 3. doi:10.1056/NEJMoa1509225).
Sensitivity analyses and post hoc analyses of several subgroups of patients yielded similar results. When hospitalization for heart failure and coronary revascularization procedures were added to the primary endpoint, lixisenatide still provided no cardioprotective effect compared with placebo. Mortality from any cause was not significantly different between the two study groups, at 7.0% with lixisenatide and 7.4% with placebo.
Adverse effects leading to withdrawal from the study were more common with lixisenatide (11.4%) than placebo (7.2%). In particular, treatment discontinuation due to nausea and vomiting occurred in 3.0% of patients taking active treatment, compared with 0.4% of those taking placebo.
Sanofi, maker of lixisenatide, funded the study. Dr. Pfeffer reported receiving grants and personal fees from Sanofi and 20 other drug companies; his associates reported ties to numerous industry sources.