LEADER Trial: Liraglutide Effectively Reduces Adverse CV Events

Treatment with the glucose-lowering drug liraglutide significantly reduces rates of major adverse cardiovascular events and death in patients with type 2 diabetes at elevated cardiovascular risk, according to results from the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcomes Results (LEADER) trial.

Previous research has shown that glycemic control is associated with risk reduction of microvascular complications, but its macrovascular benefits are less well understood.

To examine these potential benefits, as well as the cardiovascular safety of antihyperglycemic therapies, the US Food and Drug Administration mandated assessment of cardiovascular safety of new diabetes treatment options. The LEADER trial was initiated to explore these issues as they pertain to treatment with the glucagon-like peptide 1 analogue liraglutide.
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The researchers conducted a multicenter, double-blind, placebo-controlled trial of 9340 high-risk adults with type 2 diabetes randomly assigned to either liraglutide or placebo, with 3.5 to 5 years of follow-up. Participants had glycated hemoglobin levels of 7.0% or more and had either not received drug treatment for their condition previously or had been treated with 1 or more oral antihyperglycemic agent or insulin, or a combination of these agents. They were either 50 years old or older and had at least 1 coexisting cardiovascular condition, or age 60 years with at least 1 cardiovascular risk factor. They attended follow-up visits at 1, 3, and 6 months and every 6 months thereafter.

Overall, the primary composite outcome of first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke occurred in fewer participants in the liraglutide group than in the placebo group (608 of 4668 vs 694 of 4672, respectively).

Death occurred in fewer participants in the liraglutide group, as did nonfatal myocardial infarction and nonfatal stroke, although the difference was not significant.

Weight loss and heart rate were higher and systolic and diastolic blood pressure lower in the liraglutide group than in the placebo group.

“In conclusion, among patients with type 2 diabetes who were at high risk for cardiovascular events while they were taking standard therapy, those in the liraglutide group had lower rates of cardiovascular events and death from any cause than did those in the placebo group,” the authors wrote.

—Michael Potts

Reference:
Marso SP, Daniels GH, Brown-Frandsen K, et al; LEADER Steering Committee on behalf of the LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes [published online June 13, 2016]. N Engl J Med. doi:10.1056/NEJMoa1603827