At a glance

What is enlicitide?

Enlicitide (development code MK-0616) is a cholesterol-lowering drug that blocks PCSK9, a protein that controls how the liver clears LDL cholesterol from the blood. It is notable as the first oral PCSK9 inhibitor: earlier drugs against this target are injectable antibodies or an injectable RNA therapy, while enlicitide is a specially engineered peptide taken as a once-daily tablet. It is made by Merck and sold under the brand name Lipfendra.

How does it work?

Enlicitide binds circulating PCSK9¹ and stops it from attaching to the LDL receptor on liver cells. Normally PCSK9 marks those receptors for destruction, so blocking it lets more LDL receptors return to the cell surface and recycle. With more receptors available, the liver pulls more LDL cholesterol out of the blood, lowering LDL levels. Achieving this with a peptide small and stable enough to survive oral dosing is what distinguishes enlicitide from the injectable drugs in its class.

Is it FDA-approved?

Yes. The FDA approved² enlicitide in 2026 as Lipfendra, a once-daily oral PCSK9 inhibitor to reduce LDL cholesterol in adults with high cholesterol. A cardiovascular outcomes trial, testing whether the LDL lowering translates into fewer heart attacks and strokes, was reported to be ongoing at approval.

What is it prescribed for?

Enlicitide is prescribed, alongside diet and exercise, to lower LDL cholesterol in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia³ (HeFH), an inherited form of high cholesterol. In its pivotal trials¹ it was added to existing cholesterol-lowering treatment, usually a statin, in people who still needed further lowering. It offers an oral option for people who would otherwise need an injectable PCSK9 inhibitor to reach their LDL goals. It is taken under the direction of a clinician as part of overall cardiovascular risk management.

What are the side effects?

In the larger Phase 3 trial, CORALreef Lipids, side effects occurred at similar rates¹ with enlicitide and placebo. In the trial of adults with HeFH, the most common³ side effects reported more often than with placebo were:

• Dizziness (9% with enlicitide, 4% with placebo)
• Diarrhea (7% with enlicitide, 2% with placebo)

In both trials, similar proportions of people in the enlicitide and placebo groups stopped treatment because of a side effect. The prescribing information² advises stopping enlicitide when pregnancy is recognized unless the benefits of treatment outweigh the potential risks to the fetus. It has the full safety details, and people should review their individual risks and other medications with their prescriber.

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