Series: Cardiovascular outcome trials for diabetes drugs Liraglutide and LEADER

LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) was an FDA-mandated cardiovascular outcome trial with liraglutide and was the first trial with a glucagon-like peptide-1 (GLP-1) receptor agonist to demonstrate a significant reduction in cardiovascular events. It compared liraglutide and placebo in 9,340 people with type 2 diabetes and either existing cardiovascular disease or age >60 years with at least one cardiovascular risk factor. LEADER demonstrated superiority for major cardiovascular events (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke), and cardiovascular deaths were significantly reduced, as was all-cause mortality. Hospitalisation for heart failure, which was a secondary outcome, was not significantly reduced. Compared with the EMPA-REG OUTCOME trial, the curves for major adverse cardiovascular events in LEADER separated later, and the absence of a clear effect on hospitalisation for heart failure or on estimated glomerular filtration rate suggests that the mechanism of cardiovascular benefit for liraglutide was different from that for empagliflozin