LEADER trial (revision 6)

LEADER was a randomised, double-blind, placebo-controlled cardiovascular outcome trial of liraglutide in 9,340 adults with type 2 diabetes at high cardiovascular risk, followed for a median 3.8 years.^[1]

The primary composite outcome occurred in 13.0% of the liraglutide group and 14.9% of the placebo group, a hazard ratio of 0.87 (95% CI 0.78–0.97). Cardiovascular death was reduced, and all-cause mortality was lower in the liraglutide group.^[1]

It was among the first trials to show that an incretin therapy could reduce cardiovascular events rather than merely not increase them, at a time when such trials were being run principally to exclude harm.^[1]

Cardiovascular outcome trials for glucose-lowering drugs were mandated by regulators following concerns about an earlier drug class, and were designed as non-inferiority trials to exclude excess risk. LEADER was designed on that basis and tested for superiority in a pre-specified hierarchy after non-inferiority was established.^[1]

The population was enriched for events: participants were 50 or older with established cardiovascular, cerebrovascular or renal disease, or 60 or older with risk factors. Enrichment increases the event rate and therefore the power of a trial of a given size, and it also limits generalisation to lower-risk populations.^[2]

Background therapy was standard care, so as in SELECT the effect measured is incremental to contemporary treatment.