Cardiovascular safety of liraglutide and semaglutide. Clinical comments to the discussed trials LEADER and SUSTAIN 6
Abstract
The LEADER trial assessed the cardiovascular safety of liraglutide, moderate-acting GLP-1 receptor agonist. In total, 9 340 participants were randomized.
Liraglutide treatment was associated with significant reduction in composite endpoint (MACE, cardiovascular death, stroke, myocardial infarction) by 13% (hazard ratio [HR] 0.87; 95% confidence interval [CI] 0.78-0.97; p < 0.001 for non-inferiority; p = 0.01 for superiority), cardiovascular mortality by 22% (HR 0.78; 95% CI 0.66-0.93; p = 0.007), and all-cause mortality to a similar extent (HR 0.85; 95% CI 0.74-0.97; p = 0.02). The SUSTAIN trial assessed the cardiovascular safety of semaglutide, long-acting GLP-1 receptor agonist.
In total, 3 297 participants were randomized. During the 104 weeks of the trial duration, the primary endpoint (MACE) occurred in 8.9% patients in the placebo arm and in 6.6% patients in the active treatment arm (HR 0.74; CI 0.58-0.95; p = 0.02 for superiority, p < 0.001 for non-inferiority).
Cardiovascular death was recorded in 2.8% patients in the placebo arm and in 2.7% patients in the active treatment arm (HR 0.98; CI 0.65-1.48; p = 0.92). Both liraglutide and semaglutide lowered the risk of cardiovascular events in patients with type 2 diabetes, as assessed by trials evaluation cardiovascular safety.