NEW ORLEANS—Earlier this year, Novo Nordisk’s Victoza became the second diabetes drug to lower cardiovascular risks in a clinical trial. Now, we know by just how much.
In a strictly embargoed batch of data, Victoza took a 13% bite out of the combined risk of heart attack, stroke and death from cardiovascular causes, among patients who came into the trial with established cardiovascular disease. That composite endpoint, known as MACE, was the LEADER trial’s primary measure.
The placebo-controlled study assessed a range of other endpoints, and Victoza delivered statistically significant reductions on some of those as well, with a 22% lower risk of cardiovascular death; a 15% lower risk of death, period; and a 22% lower risk of advanced diabetic kidney disease. The MACE was driven by decreases in heart attacks and strokes as well as CV death.
The study results show “that liraglutide can safely improve outcomes beyond the core treatment of type 2 diabetes,” lead investigator John Buse of the University of North Carolina School of Medicine said as the results were announced.
The drug “reduced the risk of the most serious complications associated with type 2 diabetes, including the risk of death,” Buse added.
The Novo ($NVO) drug is the first GLP-1 to demonstrate a cardiovascular benefit. In an outcomes trial, Sanofi’s ($SNY) GLP-1 lixisenatide did not increase CV risks, but did not lower them, either.
“We know it is not a class-wide effect,” Dr. Todd Hobbs, Novo’s chief medical officer, told FiercePharma at the American Diabetes Association’s Scientific Sessions. “So far, it is specific to liraglutide,” though top-line data on Novo’s weekly GLP-1 drug semaglutide recently showed a statistically significant decrease in CV risks as well.
Victoza’s risk-reduction feat follows Eli Lilly ($LLY) and Boehringer Ingelheim’s EMPA-REG outcomes trial, in which their SGLT-2 drug Jardiance reduced the MACE risk by 14% and cut cardiovascular death risk by 38%. Though other SGLT-2 drugs are still undergoing their own heart-risk trials, researchers suggest that the entire group may deliver CV benefits.
Details from the SUSTAIN-6 outcomes study on semaglutide will be presented later this year.
LEADER enrolled 9,340 patients at high risk for heart disease and followed them for an average of 3.8 years. Those in the Victoza arm were titrated up to a 1.8-mg dose, based on tolerance. The participants were 64 years old, on average, and 73% had previously diagnosed cardiovascular disease. Sixty-four percent of them were men.
No significant safety issues cropped up in the Victoza patients, either, the American Diabetes Association said in a release announcing the results.
The LEADER results were the headline event at the American Diabetes Association Scientific Sessions this year. They were presented on Monday afternoon and were simultaneously published in the New England Journal of Medicine.
Since Lilly and Boehringer unveiled their Jardiance results, experts have argued about the mechanisms behind the reduced risk of death. Could it be the diuretic effects of the drug, given that diuretics are often given to patients with heart disease? Or the effects on blood pressure, blood glucose, lipids--or a combination of all of them?
Similar questions will apply to Victoza now that the LEADER data is public, Hobbs said. “The data is good,” he said. “Now the debate will ensue over why.”
- read the LEADER release
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