Novo Nordisk today announced top-line positive results of the LEADERS trial, the cardiovascular outcomes trial testing its diabetes drug Victoza (liraglutide). Liraglutide is a GLP-1 inhibitor used to help achieve glucose control in patients with type 2 diabetes.
9,340 people with type 2 diabetes were randomized to liraglutide or placebo in LEADERS for 3.5 – 5 years. The trial’s primary endpoint was the composite outcome of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke.
The company said that the placebo-controlled trial had met the primary endpoint of showing non-inferiority and had also demonstrated “a statistically significant reduction in cardiovascular risk.” The company said that “the superior reduction of major adverse cardiovascular events… was derived from all three components of the endpoint.” The safety profile of the drug in the trial “was generally consistent with previous liraglutide clinical studies.”
Full details of the trial will be presented in June at the annual meeting of the American Diabetes Association.
LEADERS is now the third diabetes drug to announce positive results from a cardiovascular outcomes trial. For a long time there was considerable controversy over the lack of outcomes data for the growing number of diabetes drugs on the market. Then several trials showed noninferiority but were unable to demonstrate benefit in clinical outcomes. Last year the EMPA REG trial showed clinical benefit with empagiflozin. Last month the IRIS trial showed that pioglitazone reduced events in patients with stroke.
Sanjay Kaul (Cedars Sinai) said that the results of these trials “clearly vindicates the 2008 FDA guidance (at least in the case of EMPA and LEADERS) that requires the sponsors to conduct cardiovascular outcomes trials to rule out unacceptable risk.”
Kaul said he was eager to learn the full results of the trial. “Announcing that the results are positive is fine, but I would like to know what was the magnitude of benefit and whether it was statistically robust. Lack of heterogeneity of treatment effect across the individual components of the primary composite endpoint sets it apart from the EMPA REG OUTCOME trial results where the stroke outcome point estimate does not favor empagliflozin.”
Kaul said he was also waiting to see more safety data from the trial. “I would like to have seen more details about pancreatic and thyroid adverse events. Previous studies have shown a numerical imbalance in these events not favoring liraglutide.”