ADA: Liraglutide Reduces Risk of Heart Events
Widely-anticipated cardiovascular outcomes trial delivers positive result.
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Note that this large, randomized trial of liraglutide versus placebo as add-on therapy to standard-of-care diabetes medication demonstrated that the GLP-1 analogue reduced the risk of overall mortality and cardiovascular events.
Be aware that there was no difference in weight-loss between the two arms of the study.
In the greatly anticipated LEADER trial, Bernard Zinman, MD, of the University of Toronto, reported that treatment with the injectable agent liraglutide was associated with a 13% relative risk reduction in major adverse coronary events -- a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke (P=0.01).
At a press conference, he said that the absolute difference in outcome for preventing a coronary event was 1.9
As moderator of the press conference, Robert Eckel, MD, a member of the American Diabetes Association Board of Directors and professor of medicine at the University of Colorado School of Medicine in Aurora, said, "LEADER is a complicated study but it may have an impact on practice."
He told MedPage Today that liraglutide may fit into the treatment algorithm when doctors consider what to prescribe for patients who can't reach their HbA1c goals on metformin, the generally accepted first-line treatment.
"But now with EMPA-REG, published a year ago, and now with LEADER we have to think beyond metformin as to what that second drug of choice might be.
With LEADER we already have a hint that there may be another drug in this class that appears to be beneficial," Eckel said.
"I think, ultimately, validation of these results is needed for this to change practice.
I think that if my patients needs to lose weight, I am going to think in terms of a drug that causes weight loss in addition to controlling glycemia. I would like to see second and third trials with both of these drugs -- liraglutide and empagliflozin," he added.
Eckel suggested that the results in LEADER indicate that the benefit may come from the overall ability of the treatment to affect multiple factors.
"LEADER gives me a hint of a lot of modifiable risk factors for cardiovascular disease -- a little bit lower systolic blood pressure, lower waist circumference, lower body weight -- lots of things related to cardiovascular disease risk," he explained. "Everything is sort of changing modestly in the right direction. Is it the modest HbA1c reduction? Or is it some composite advantage and everything is additive to something else?"
However, Eckel said that the high number to treat takes some wind out of LEADERS's sails.
"We rather crudely use 50 as the number to treat as the goal for many interventions, so the issue that comes up next with liraglutide is one of cost," he said.
A Targeted Patient-Centered Approach
Mean patient age was 64, and 64% of the cohort were men. The patients had been diagnosed with diabetes for almost 13 years before entering the trial.
About 355 of the patients were Europeans; another 30% were from North America. Their baseline HbA1c averaged 8.7% and mean baseline body mass index was 32.5 kg/m2; their average body weight was about 92 kg. About 18% of the patients in both arms of the trial had been diagnosed with heart failure.
Zinman reported that after 36 months, the difference in HbA1c was about 0.4 percentage points lower in the liraglutide patients versus the placebo group, a difference that was statistically significant (P<0.01). The placebo patients had lowered their HbA1c from 8.7% to about 8%; the liraglutide patients had lowered their HbA1c from 8.7% to about 7.6%.
Patients on liraglutide achieved a mean 2.3-kg reduction in body weight during the 3-year study with a similar decrease among the placebo patients, Zinman said.