Lipid-efficacy RCT · N Engl J Med 2026
CORALreef Lipids trial
A Placebo-Controlled Trial of the Oral PCSK9 Inhibitor Enlicitide.
The bottom line
In patients with or at risk for atherosclerotic cardiovascular disease, the oral PCSK9 inhibitor enlicitide substantially lowered LDL cholesterol and other atherogenic lipid markers compared with placebo, with adverse event rates similar between groups.
Primary lipid endpoint metUS status: US-approved
At a glance
- Medicine
- Enlicitide decanoate (oral PCSK9 inhibitor), 20 mg daily for 52 weeks
- Compared with
- Placebo
- People
- 2,909
- Who took part
- Adults with a history of a major atherosclerotic cardiovascular disease event with an LDL cholesterol level of 55 mg per deciliter or higher and those who were at risk for a first atherosclerotic cardiovascular disease event with an LDL cholesterol level of 70 mg per deciliter or higher
- Design
- multinational, double-blind, randomized, placebo-controlled trial
- Follow-up
- 52 weeks
- Main question
- Mean percent change in LDL cholesterol level from baseline to week 24
Main result
The mean percent change in LDL cholesterol levels at week 24 was -57.1% (95% confidence interval [CI], -61.8 to -52.5) with enlicitide and 3.0% (95% CI, 0.9 to 5.1) with placebo, representing an adjusted between-group difference of -55.8 percentage points (95% CI, -60.9 to -50.7; P<0.001)
Effect on LDL cholesterol
-57.1% (95% CI, -61.8 to -52.5) with enlicitide vs 3.0% (95% CI, 0.9 to 5.1) with placebo; adjusted between-group difference -55.8 percentage points (95% CI, -60.9 to -50.7; P<0.001)
Other results
The mean percent change in LDL cholesterol level at week 52, the mean percent changes in non-HDL cholesterol and apolipoprotein B levels at week 24, and the percent change in lipoprotein(a) levels at week 24 were significantly greater with enlicitide than with placebo (P<0.001 for all comparisons).
Safety
The incidence of adverse events did not appear to differ between the groups.
In the trial's own words
“The mean percent change in LDL cholesterol levels at week 24 was -57.1% (95% confidence interval [CI], -61.8 to -52.5) with enlicitide and 3.0% (95% CI, 0.9 to 5.1) with placebo, representing an adjusted between-group difference of -55.8 percentage points (95% CI, -60.9 to -50.7; P<0.001).”
Quoted from the abstract of N Engl J Med 2026, checked word for word against PubMed. PubMed 41879224 · Full paper (DOI)
How this medicine works, where it stands and what it costs: Enlicitide (Lipfendra)
Common questions
What did the CORALreef Lipids trial find?
In patients with or at risk for atherosclerotic cardiovascular disease, the oral PCSK9 inhibitor enlicitide substantially lowered LDL cholesterol and other atherogenic lipid markers compared with placebo, with adverse event rates similar between groups.
Who was in CORALreef Lipids?
2,909 people. Adults with a history of a major atherosclerotic cardiovascular disease event with an LDL cholesterol level of 55 mg per deciliter or higher and those who were at risk for a first atherosclerotic cardiovascular disease event with an LDL cholesterol level of 70 mg per deciliter or higher.
What was CORALreef Lipids's main result?
The mean percent change in LDL cholesterol levels at week 24 was -57.1% (95% confidence interval [CI], -61.8 to -52.5) with enlicitide and 3.0% (95% CI, 0.9 to 5.1) with placebo, representing an adjusted between-group difference of -55.8 percentage points (95% CI, -60.9 to -50.7; P<0.001)
How much did LDL cholesterol change in CORALreef Lipids?
-57.1% (95% CI, -61.8 to -52.5) with enlicitide vs 3.0% (95% CI, 0.9 to 5.1) with placebo; adjusted between-group difference -55.8 percentage points (95% CI, -60.9 to -50.7; P<0.001)
Related trials
- CORALreef HeFH (2026)In patients with heterozygous familial hypercholesterolemia already on statin therapy, adding oral enlicitide substantially and safely lowered LDL-C and other atherogenic lipid measures compared with placebo.
- VESALIUS-CV (2026)In patients with atherosclerosis or diabetes but no prior MI or stroke, adding evolocumab to therapy significantly lowered the risk of major cardiovascular events compared with placebo, with no apparent safety concerns.
- PURSUIT (2025)In statin-treated patients with hypercholesterolemia, the oral PCSK9 inhibitor AZD0780 produced robust, dose-dependent LDL-C reductions over 12 weeks with an adverse event rate similar to placebo.
- LIBerate-HR (2024)Monthly lerodalcibep added to maximally tolerated statins substantially lowers LDL-C and helps most high-risk patients reach guideline LDL-C targets, with a safety profile similar to placebo aside from mild/moderate injection site reactions.
Get your LDL treated to a goal
Preval Health's protocols follow trials like this one. Licensed clinicians set your goal, prescribe and recheck until you reach it.
Get startedEducation only, not medical advice. Results describe the people in this trial and can differ for you. Talk with your clinician before starting or stopping any medicine. Back to all 106 trials.