- Question
- Does enlicitide, an oral PCSK9 inhibitor, lower LDL cholesterol compared with placebo in adults with a history of atherosclerotic cardiovascular disease or at risk for a first event, and is the effect sustained at one year?
- Design
- Multinational, double-blind, randomized, placebo-controlled trial with 2:1 allocation and 52 weeks of treatment. The intention-to-treat population included 2909 participants (1935 on enlicitide and 969 on placebo); the registry reports 2912 enrolled.
- Population
- Adults with a prior major atherosclerotic cardiovascular event and LDL cholesterol of 55 mg/dL or higher, or adults at risk for a first event with LDL cholesterol of 70 mg/dL or higher. Mean age was 63 years, 39.3% were women, and mean baseline LDL cholesterol was 96.1±38.9 mg/dL.
- Intervention
- Enlicitide 20 mg orally once daily for 52 weeks.
- Control
- Matching oral placebo once daily for 52 weeks.
- Primary outcome
- Mean percent change in LDL cholesterol from baseline to week 24.
- Results
- At week 24, LDL cholesterol changed by -57.1% (95% CI, -61.8 to -52.5) with enlicitide and 3.0% (95% CI, 0.9 to 5.1) with placebo, an adjusted between-group difference of -55.8 percentage points (95% CI, -60.9 to -50.7; P<0.001). The week 52 LDL cholesterol change, the week 24 changes in non-HDL cholesterol and apolipoprotein B, and the week 24 change in lipoprotein(a) were also significantly greater with enlicitide (P<0.001 for all comparisons).
- Safety
- The incidence of adverse events did not appear to differ between the groups.
- Conclusion
- In patients with a history of atherosclerotic cardiovascular disease or at risk for a first event, enlicitide significantly lowered LDL cholesterol compared with placebo at 24 weeks.
- Why it matters
- It showed that a PCSK9 inhibitor taken by mouth can achieve deep LDL cholesterol reductions, opening the possibility of an alternative to injectable drugs in this class.
Card generated automatically with AI from the abstract of the original publication and the trial registry; every figure was checked against those sources. It may contain errors: verify the data at the source before using it for clinical decisions.
Generated on October 14, 2026