Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial was a multicentre, international, randomised, double-blind, placebo-controlled trial investigating the long-term effects of liraglutide 1.2 and 1.8 mg compared to placebo, both in addition to standard of care, in people with type 2 diabetes (T2DM) at high risk of cardiovascular events. The trial was initiated in September 2010 and randomised 9,340 people with T2DM from 32 countries that were followed for 3.5–5 years. In Australia, 222 patients from 10 trial sites were randomised and completed the study. The primary endpoint of the study was the first occurrence of a composite cardiovascular outcome comprising cardiovascular death (CVD), non-fatal myocardial infarction (MI) or non-fatal stroke.
The primary outcome was significantly lower in the liraglutide group (13.0%) than in the placebo group (14.9%) (HR, 0.87; 95% CI, 0.78 to 0.97; P<0.001 for non-inferiority; P = 0.01 for superiority). Fewer patients died from cardiovascular causes in the liraglutide group (4.7%) than in the placebo group (6.0%) (HR, 0.78; 95% CI, 0.66 to 0.93; P = 0.007). The rate of death from any cause was lower in the liraglutide group (8.2%) than in the placebo group (9.6%) (HR, 0.85; 95% CI, 0.74 to 0.97; P = 0.02). The rates of nonfatal MI, nonfatal stroke, and hospitalisation for heart failure were non-significantly lower in the liraglutide group than in the placebo group. The most common adverse events leading to the discontinuation of liraglutide were gastrointestinal events. The incidence of pancreatitis was non-significantly lower in the liraglutide group than in the placebo group.
Rates of cardiovascular events and death from any cause were lower among patients with T2DM and at high risk for cardiovascular events while on liraglutide and taking standard therapy, compared with those in the placebo group.