Lixisenatide shows no heart benefit and no harm in 6,068-patient ELIXA trial
The ELIXA trial found lixisenatide neither raised nor lowered the risk of heart attack, stroke or cardiovascular death in people with type 2 diabetes after a recent acute coronary event.
Lixisenatide did not change the rate of major cardiovascular events in people with type 2 diabetes who had recently had a heart attack or been hospitalized for unstable angina, according to the results of the ELIXA trial. The drug showed neither benefit nor harm on the trial's main heart-related measure [1].
ELIXA randomly assigned 6,068 patients with type 2 diabetes who had had a myocardial infarction or been hospitalized for unstable angina within the previous 180 days. They received lixisenatide or placebo on top of locally determined standard care and were followed for a median of 25 months [1].
What the trial measured
The main measure combined four outcomes: cardiovascular death, myocardial infarction, stroke, or hospitalization for unstable angina. The trial was built to answer two questions at once — whether lixisenatide was noninferior to placebo (no worse by more than a set margin) and whether it was superior to placebo. The statistical thresholds were an upper boundary of the 95% confidence interval for the hazard ratio below 1.3 for noninferiority and below 1.0 for superiority [1].
A primary endpoint event occurred in 406 patients taking lixisenatide (13.4%) and 399 taking placebo (13.2%). The hazard ratio was 1.02, with a 95% confidence interval of 0.89 to 1.17. That showed noninferiority (P<0.001) but not superiority (P=0.81) [1].
Other outcomes pointed the same way. Hospitalization for heart failure occurred at a hazard ratio of 0.96 (95% CI, 0.75 to 1.23), and death at a hazard ratio of 0.94 (95% CI, 0.78 to 1.13). Neither difference was statistically significant [1].
The report also said lixisenatide was not associated with higher rates of serious adverse events, severe hypoglycemia, pancreatitis, pancreatic neoplasms, or allergic reactions than placebo [1]. The trial was funded by Sanofi and registered as NCT01147250 [1].
Why it matters for patients
ELIXA was designed around a practical question for people with type 2 diabetes: does this medicine change the odds of a heart attack, a stroke, or death from heart disease? For the patients studied — people who had just come through a heart attack or a hospitalization for unstable angina — the rate of those events was essentially the same as with placebo [1].
The group studied is a specific, high-risk one: everyone enrolled had had an acute coronary event within the previous 180 days [1]. How the findings apply to people with type 2 diabetes who have not had a recent heart event has not been reported from this trial.
The trial measured cardiovascular events and safety. It did not report weight or blood sugar outcomes in this paper [1].
The findings cover lixisenatide only. Whether other GLP-1 receptor agonists behave the same way on cardiovascular outcomes is not established by this trial [1].
No US regulatory action, label change, or change in insurance coverage tied to these results has been disclosed [1].
What happens next
Follow-up discussion of the trial is appearing in the medical literature. Nature Reviews Cardiology published a commentary titled "Diabetes: Lixisenatide does not increase rates of CVD events" in its February 2016 issue, posted online Dec. 24, 2015, and the New England Journal of Medicine published correspondence on the trial on March 17, 2016 [1]. No further results from ELIXA, and no regulatory decisions based on them, have been disclosed [1].
Sources
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