LEADER trial (revision 3)
Old revision·16:25, 20 Sep 2024·FlowTrialFraser
| LEADER trial | |
|---|---|
| Drug | Liraglutide up to 1.8 mg daily |
| Population | Type 2 diabetes, high cardiovascular risk |
| Participants | 9,340 |
| Primary result | MACE HR 0.87 (95% CI 0.78–0.97) |
| Topic infobox · conventions | |
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]
Design and context
[edit]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]
References
- ^ a b c Marso SP, Daniels GH, Brown-Frandsen K, et al. "Liraglutide and cardiovascular outcomes in type 2 diabetes." New England Journal of Medicine 375(4):311–322 (2016). DOI:10.1056/NEJMoa1603827. PMID 27295427.
- ^ International Council for Harmonisation, E9(R1): Estimands and Sensitivity Analysis in Clinical Trials (2019).