First oral PCSK9 inhibitor in pill form. Lowers LDL cholesterol in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia.
FDA (US): Approved (July 2026, Lipfendra) to lower LDL cholesterol, alongside diet and exercise, in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia.
EMA (EU): Not approved (no authorization in the EU as of October 2026).
Dose
20 mg orally once a day (FDA 2026 prescribing information; CORALreef trials).
Safety
In the main trial, the frequency of adverse effects was similar to placebo. In the familial hypercholesterolemia trial there was somewhat more diarrhea (7% vs 2%) and dizziness (9% vs 4%), without a significant difference. No published data yet on reduction of heart attacks. Requires a prescription.
Effect by goal · level of evidence
LDL cholesterol in hypercholesterolemia
reducesHighRCT (AA)in people
−56% LDL
CORALreef Lipids trial (2,909 adults, 39% women): at 24 weeks LDL fell by 57.1% with enlicitide vs a 3.0% rise with placebo (difference −55.8 points). It also reduced lipoprotein(a).
PCSK9 is a protein that destroys LDL cholesterol receptors in the liver. Enlicitide is a cyclic peptide designed to resist digestion that binds to PCSK9 and blocks it. This way the liver keeps more receptors and clears more LDL cholesterol from the blood.
What the evidence says
In people
LDL cholesterol in hypercholesterolemia. CORALreef Lipids trial (2,909 adults, 39% women): at 24 weeks LDL fell by 57.1% with enlicitide vs a rise of 3.0% with placebo (difference −55.8 points). It also reduced lipoprotein(a). PubMed 41879224