Liraglutide Significantly Cuts Heart Risk, LEADER Trial Shows

Data from the LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results-A Long Term Evaluation) trial showed a reduction in major cardiovascular events with the glucose-lowering drug liraglutide (Victoza; Novo Nordisk) in adults with type 2 diabetes at elevated cardiovascular risk. The findings were presented during a 2-hour special symposium at the American Diabetes Association’s (ADA) 76th Scientific Sessions (June 10-14, 2016; New Orleans, LA) devoted to the findings and were simultaneously published online (N Engl J Med. published online June 13, 2016; doi:10.1056/NEJMoa1603827).

LEADER is the longest trial to date to report cardiovascular outcomes for diabetes medications. “Our results should give patients and providers more comfort that liraglutide can safely improve outcomes beyond the core treatment of type 2 diabetes,” said lead investigator John B Buse, MD, PhD, University of North Carolina School of Medicine, Chapel Hill, in a press statement. “In addition, liraglutide reduced the risk of the most serious complications associated with type 2 diabetes, including risk of death. It is exciting to see such broad-based benefit for patients who took liraglutide because most prior trials of diabetes medications have not shown such benefits.”

The multicenter, randomized, double-blind, placebo-controlled study began in 2010 and enrolled participants with type 2 diabetes with glycated hemoglobin levels of 7.0% or higher who either had a prior cardiovascular event or were at high risk for cardiovascular events based on age and other risk factors. Patients in both groups were drug treatment naïve or were treated with oral antihyperglyemic agents, selected insulins, or a combination of agents. Participants who had a prior cardiovascular event were aged 50 or older and had least 1 coexisting comorbidity. Participants who had no prior cardiovascular events at baseline were aged 60 or older with cardiovascular risk factors.

The 9340 participants included in the study were randomized 1:1 to once-daily subcutaneous liraglutide 1.8 mg or the maximum tolerated dose (n = 4668) or placebo (n = 4672) along with standard treatment and were followed for an average of 3.8 years. The primary endpoint was the first occurrence of the 3-point major adverse cardiac event (MACE) components: cardiovascular death, nonfatal myocardial infarction (MI), or nonfatal stroke.

The degree of risk reduction for MACE was lower in the liraglutide group vs the placebo group (13.0% vs 14.9%, respectively). Overall, the results for each of the components of the composite primary MACE outcome were better with liraglutide, with a 22% lower risk of cardiovascular death (4.7% vs 6.0%, respectively; P = .007), a 12% reduction in nonfatal MI (6.0% vs 6.8%; P = .11), and an 11% lower rate of nonfatal stroke (3.4% vs 3.8%; P = .30). Participants in the liraglutide arm also had a 15% lower risk of all-cause mortality (8.2% vs 9.6%; P = .02). 

No significant safety issues were observed among the participants in the liraglutide group, with gastrointestinal adverse events and increases in heart rate being the most common, according to the results. Overall adverse events occurred in both the liraglutide and placebo arms but were not significantly different (62.3% vs 60.8%, respectively). Serious adverse events occurred in 49.7% and 50.4% of participants, and severe adverse events occurred in 32.2% and 32.8% of participants, in the liraglutide and placebo arms, respectively.—Eileen Koutnik-Fotopoulos