A large clinical trial reports significant reductions in LDL
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An experimental pill called enlicitide was found to dramatically lower LDL (bad) cholesterol by ~60% in a large phase 3 clinical trial.
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The study enrolled nearly 2,900 adults already on statins who still had elevated LDL levels despite treatment.
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Beyond LDL, the pill improved other heart-disease-linked lipids, with safety similar to placebo.
High levels of low-density lipoprotein (LDL) cholesterol often called bad cholesterol build up in artery walls and can lead to heart attacks and strokes.
Lowering LDL is a cornerstone of heart disease prevention, especially for people with atherosclerotic cardiovascular disease or those at elevated risk. Statins, the most common cholesterol pills, do this well for many people, but not all patients reach recommended LDL goals even when taking them.
Enter enlicitide, an experimental oral medication that targets a protein called PCSK9 in the bloodstream. PCSK9 normally makes it harder for the liver to clear LDL cholesterol; by blocking it, the body can remove more LDL from circulation.
Fewer than half of patients with established atherosclerotic cardiovascular disease currently reach LDL cholesterol goal, researcher Ann Marie Navar, M.D., Ph.D. said in a news release.
An oral therapy this effective has the potential to dramatically improve our ability to prevent heart attacks and strokes on a population level.
The study
The Phase 3 CORALreef Lipids trial was designed to test whether enlicitide could safely and effectively lower LDL cholesterol compared with a dummy pill (placebo).
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Who participated: 2,909 adults aged roughly 63 on average, with either a history of a major cardiovascular event or a high risk of one, despite being on statins.
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What happened: Participants were randomly assigned in a 2:1 ratio to take once-daily enlicitide (20 mg) or placebo, with background lipid-lowering therapy maintained.
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Primary goal: Measure how much LDL cholesterol changed after 24 weeks. Secondary measures included other lipid markers and results at 52 weeks.
Importantly, neither the participants nor the clinicians knew who was getting the real drug vs. placebo during the trial a setup that helps keep the results unbiased.
What the results showed
After 24 weeks, the people taking enlicitide saw their LDL levels fall by an average of about 57%, compared with a slight rise in the placebo group a striking difference.
Beyond LDL cholesterol, enlicitide also significantly reduced other lipids linked with heart disease risk:
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Non-HDL cholesterol dropped by over 50%.
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Apolipoprotein B (a marker of bad cholesterol particles) fell by about 50%.
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Lipoprotein(a) declined by roughly 28%.
A large proportion of people taking enlicitide reached guideline-recommended LDL goals that are associated with lower cardiovascular risk.
Importantly, rates of side effects were similar between the drug and placebo groups during the yearlong study, suggesting that the pill was generally well tolerated.
These reductions in LDL cholesterol are the most we have ever achieved with an oral drug by far since the development of statins, Dr. Navar said.
Posted: 2026-02-12 19:23:28

















