Digestive & weight Oral macrocyclic PCSK9 inhibitor peptide
Enlicitide
Regulatory status
Status at a glance
503A compounding status
Not nominated
We found no pending nomination for the 503A bulks list. Unless the substance has another legal pathway (for example, a USP monograph or use in an FDA-approved drug), 503A pharmacies generally may not compound with it.
- FDA approval
- An FDA-approved product contains this peptide
- 503B outsourcing
- Not determined
- Anti-doping (WADA)
- Not on the WADA Prohibited List
- DEA schedule
- Not a controlled substance
About peptide status
Most peptides discussed here are not FDA-approved for any use, and products labeled “research use only” are not for human use. Removal from Category 2 does not authorize compounding. PCAC votes are non-binding recommendations; FDA and HHS make the final decisions.
This is not medical or legal advice, and we do not publish dosing, sourcing or reconstitution information. Talk with a licensed clinician before using any peptide.
If you think you are having a medical emergency, call 911.
Key takeaway
Enlicitide is an oral PCSK9 inhibitor, the first in its class that can be taken as a once-daily tablet rather than an injection, developed by Merck to lower LDL ("bad") cholesterol. In large Phase 3 trials it lowered LDL cholesterol by roughly 60%, comparable to injectable PCSK9 antibodies. It was approved by the FDA in 2026 under the brand name Lipfendra.
At a glance
- FDA status
- FDA-approved oral PCSK9 inhibitor, sold as Lipfendra, taken as a once-daily tablet
- What it is
- Macrocyclic peptide that blocks PCSK9, the first oral drug in a class previously limited to injections
- Research
- In Phase 3 trials, lowered LDL cholesterol by about 60%
- Main uses
- Reducing LDL cholesterol in adults with high cholesterol
- Evidence strength
- FDA approved
Summary
Enlicitide (Lipfendra) is a once-daily oral PCSK9 inhibitor for lowering LDL cholesterol. Learn how it works, what Phase 3 trials showed, and its FDA status.
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 PCSK9 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?
Editor’s note
Status: FDA-approved oral PCSK9 inhibitor, sold as Lipfendra, taken as a once-daily tablet
Category: In clinical trials · Primary body area: Digestive & weight
Yes. The FDA approved 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 hypercholesterolemia (HeFH), an inherited form of high cholesterol. In its pivotal trials 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 rates with enlicitide and placebo. In the trial of adults with HeFH, the most common 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 information 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.
Sources: the CORALreef Lipids Phase 3 trial (Navar et al., New England Journal of Medicine, 2026, DOI: 10.1056/NEJMoa2511002) and an active-comparator Phase 3 trial (Catapano et al., Journal of the American College of Cardiology, 2026, DOI: 10.1016/j.jacc.2026.03.036), both indexed on PubMed; and the FDA approval announcement and prescribing information for Lipfendra. This document is educational and does not constitute medical advice.
Registered human trials
0 registered human trials on ClinicalTrials.gov that we reviewed
Sources
- [1]
- [2]
approved (PDF)
- [3]
- [4]
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