GLP-1 receptor agonists
1. Liraglutide,
① LEADER trial (n = 9,340), compared with placebo over 3.8 years
② ARR of 1.9% with a hazard ratio (HR) of 0.87 (95% CI 0.78, 0.97; P = 0.01 for superiority) for the primary composite outcome of cardiovascular death, nonfatal MI, and nonfatal stroke (major adverse cardiac events [MACE]).
③ HR for cardiovascular death was 0.78 (95% CI 0.66, 0.93; P = 0.007; ARR 1.7%).
④ HR of 0.85 (95% CI, 0.74, 0.97; P = 0.02; ARR 1.4%) for all-cause mortality (47).
2. Semaglutide
① SUSTAIN 6 (n = 3,297), compared with placebo over 2.1 years
② ARR of 2.3% with HR 0.74 for MACE (95% CI 0.58, 0.95; P = 0.02 for superiority) o
The reduction in events appeared to be driven by the rate of stroke rather than CVD death.
3. Exenatide
① EXSCEL(n = 14,752), compared exenatide extended-release with placebo over 3.2 years
Safe (noninferior), the HR for MACE in the entire trial was 0.91 (95% CI 0.83, 1.0; P =0.06)
Not reaching the threshold for demonstrated superiority versus placebo; ARR was 0.8%.
4. Lixisenatide, a short-acting GLP-1 receptor agonist
① Did not demonstrate CVD benefit or harm in a trial of patients recruited within 180 days of an
acute coronary syndrome admission.
Taken together, it appears that among patients with established CVD,
some GLP- 1 receptor agonists may provide cardiovascular benefit,
with the evidence of benefit
strongest for liraglutide,
favorable for semaglutide,
less certain for exenatide,
no evidence of cardiovascular benefit with lixisenatide.
REF.
