---
title: "Enlicitide"
canonical_url: https://peptidelibrary.app/library/enlicitide
description: "FDA-approved oral macrocyclic peptide (Lipfendra, July 2026) that blocks PCSK9 to lower LDL cholesterol in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia."
updated: 2026-10-30
publisher: Peptide Library
notice: "Research and educational use only. Not medical advice."
---

# Enlicitide

Enlicitide (also called Lipfendra or Enlicitide decanoate) is an FDA-approved oral PCSK9 inhibitor (macrocyclic peptide). Enlicitide is a macrocyclic peptide that binds PCSK9, a protein that marks LDL receptors on liver cells for degradation. By stopping PCSK9 from binding those receptors, it leaves more of them available to clear LDL cholesterol from the blood.

FDA-approved oral macrocyclic peptide (Lipfendra, July 2026) that blocks PCSK9 to lower LDL cholesterol in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia.

Also known as: Lipfendra, Enlicitide decanoate, MK-0616.

Categories: Fat Loss, GLP-1/Metabolic.

## Classification

- Type: FDA-approved oral PCSK9 inhibitor (macrocyclic peptide)
- Mechanism class: PCSK9 Inhibitor
- Development stage: Approved product
- Regulatory class: FDA-approved medicine

## Mechanism

Enlicitide is a macrocyclic peptide that binds PCSK9, a protein that marks LDL receptors on liver cells for degradation. By stopping PCSK9 from binding those receptors, it leaves more of them available to clear LDL cholesterol from the blood. Each tablet contains sodium caprate, which helps a peptide this large get absorbed, and oral bioavailability is still only about 1%.

Targets: PCSK9.

Origin: Synthetic macrocyclic peptide found by mRNA display screening and structure-based design at Merck (MSD).

## Properties

- Molecular formula: C92H129FN14O17
- Molecular weight: 1,722.12 g/mol
- CAS number: 2861205-06-1
- Half-life: Effective half-life about 14 hours; terminal half-life about 244 hours
- Studied routes: Oral

## Evidence

- Evidence level: FDA Approved
- Highest documented: Regulatory review (FDA label)
- Human trials: 6
- Controlled human trials: 5
- Preclinical sources: 1
- Latest source: 2026

Each step shows whether the sources Peptide Library has reviewed include that kind of research. Counts are reviewed sources, not every study ever published. Reviews and programme summaries that describe human use are shown as "reported", not as trials, and registered trials without published results are listed but not counted. A higher step means research has progressed further; it does not mean a compound works better or is safer. Compounds whose evidence has not been reviewed yet show "Not reviewed" instead of a guess.

### Studies

1. LIPFENDRA (enlicitide) tablets — FDA prescribing information, DailyMed. Regulatory label (FDA), human. Population: Adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia, as an adjunct to diet and exercise. Reduction of LDL cholesterol [Source](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=100ec543-fbd0-44fc-b740-db9cdff39145)
2. Navar AM et al. A Placebo-Controlled Trial of the Oral PCSK9 Inhibitor Enlicitide. N Engl J Med. 2026. 2026. Controlled human trial. Population: Adults with a past major atherosclerotic cardiovascular event or at risk of a first one, whose LDL cholesterol stayed above target on lipid-lowering treatment (1,935 on enlicitide, 969 on placebo). LDL cholesterol changed by -57.1% at week 24 versus +3.0% on placebo [Source](https://pubmed.ncbi.nlm.nih.gov/41879224/)
3. Ballantyne CM et al. Efficacy and Safety of Oral PCSK9 Inhibitor Enlicitide in Adults With Heterozygous Familial Hypercholesterolemia: A Randomized Clinical Trial. JAMA. 2026. 2026. Controlled human trial. Population: Adults with heterozygous familial hypercholesterolemia on a moderate- or high-intensity statin (202 on enlicitide, 101 on placebo). LDL cholesterol changed by -58.2% at week 24 versus +2.6% on placebo [Source](https://pubmed.ncbi.nlm.nih.gov/41206969/)
4. Catapano AL et al. Oral PCSK9 Inhibitor Enlicitide Versus Oral Nonstatin Therapies: A Phase 3 Randomized Clinical Trial. J Am Coll Cardiol. 2026. 2026. Controlled human trial. Population: Statin-treated adults needing further LDL lowering (101 on enlicitide, 200 on bempedoic acid, ezetimibe or both). LDL cholesterol changed by -64.6% versus -6.3% with bempedoic acid, -27.8% with ezetimibe and -36.5% with both [Source](https://pubmed.ncbi.nlm.nih.gov/42017875/)
5. Ballantyne CM et al. Phase 2b Randomized Trial of the Oral PCSK9 Inhibitor MK-0616. J Am Coll Cardiol. 2023. 2023. Controlled human trial. Population: Adults with hypercholesterolemia across a wide range of cardiovascular risk (n=381) [Source](https://pubmed.ncbi.nlm.nih.gov/36889610/)
6. Johns DG et al. Orally Bioavailable Macrocyclic Peptide That Inhibits Binding of PCSK9 to the Low Density Lipoprotein Receptor. Circulation. 2023. 2023. Human study (early or uncontrolled). Population: Healthy adults (single rising doses) and participants on statins (multiple doses) [Source](https://pubmed.ncbi.nlm.nih.gov/37125593/)
7. NCT06008756 — Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor) Cardiovascular Outcomes Study (CORALreef Outcomes). Controlled human trial. Population: Adults at high cardiovascular risk (estimated enrollment 14,550). Major cardiovascular events; no results yet (estimated completion 2031) [Source](https://clinicaltrials.gov/study/NCT06008756)
8. LIPFENDRA (enlicitide) tablets — FDA prescribing information, section 8.1, DailyMed. Preclinical: animal or lab study. Population: Pregnant rats and rabbits. No adverse embryofetal or maternal effects at these doses, but enlicitide crossed the placenta in rats. Limitations: Lab or animal research: not evidence of a human effect or dose. [Source](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=100ec543-fbd0-44fc-b740-db9cdff39145)

### Registered trials

- [NCT06008756](https://clinicaltrials.gov/study/NCT06008756)

## Safety

Side effects: Diarrhea (7% versus 2% on placebo, in the HeFH trial); Dizziness (9% versus 4% on placebo, in the HeFH trial); In the larger hypercholesterolemia trial, adverse reaction rates were similar to placebo.

Risks: May cause fetal harm based on how it works; the label says to stop when pregnancy is recognized unless the benefits outweigh the risks; No cardiovascular outcomes data for enlicitide yet; the outcomes trial is still running; Food cuts exposure by about half, so it depends on being taken on an empty stomach; Safety and effectiveness not established in children.

Human safety basis: FDA prescribing information

## Regulatory status

Enlicitide is an FDA-approved product for specific labelled indications. Approval does not extend to the research contexts described on this page, and approved products are prescription medicines.

- FDA status: Approved
- Availability: Prescription-Only

## Frequently asked questions

### What is enlicitide?

Enlicitide is a cholesterol-lowering medicine sold as Lipfendra. It is a macrocyclic peptide taken as a daily tablet, which sets it apart from the injectable antibody and RNA medicines that target the same PCSK9 pathway. FDA approved it in July 2026 for adults with high LDL cholesterol.

### How does enlicitide work?

Enlicitide binds PCSK9, a protein that would otherwise push LDL receptors on liver cells toward degradation. With PCSK9 blocked, more receptors stay on the liver cell surface and pull LDL cholesterol out of the blood.

### Is enlicitide FDA approved?

Yes. FDA approved enlicitide as Lipfendra on 15 July 2026 (NDA 220848, Merck Sharp & Dohme) as an adjunct to diet and exercise to reduce LDL cholesterol in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia.

### What are the side effects of enlicitide?

In the phase 3 trial of 2,904 adults, adverse reaction rates were similar to placebo. In the heterozygous familial hypercholesterolemia trial, diarrhea (7% versus 2%) and dizziness (9% versus 4%) were more common than on placebo. This is reference information, not medical advice.

### Has enlicitide been shown to prevent heart attacks?

Not yet. Its approval rests on lowering LDL cholesterol. The label notes that outcomes trials of statins and antibody PCSK9 inhibitors link lower LDL to fewer cardiovascular events, but enlicitide’s own outcomes trial, CORALreef Outcomes (NCT06008756), has not reported.

### What compounds are similar to enlicitide?

This library lists semaglutide, linaclotide and plecanatide alongside enlicitide as other peptides taken by mouth. They share a delivery route, not a target, and their uses and evidence differ.

## References

- [LIPFENDRA (enlicitide) tablets — FDA prescribing information, DailyMed](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=100ec543-fbd0-44fc-b740-db9cdff39145)
- [NDA 220848 approval letter — FDA, July 2026](https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2026/220848Orig1s000ltr.pdf)
- [A Placebo-Controlled Trial of the Oral PCSK9 Inhibitor Enlicitide — N Engl J Med, 2026](https://pubmed.ncbi.nlm.nih.gov/41879224/)
- [Efficacy and Safety of Oral PCSK9 Inhibitor Enlicitide in Adults With Heterozygous Familial Hypercholesterolemia — JAMA, 2026](https://pubmed.ncbi.nlm.nih.gov/41206969/)
- [Oral PCSK9 Inhibitor Enlicitide Versus Oral Nonstatin Therapies — J Am Coll Cardiol, 2026](https://pubmed.ncbi.nlm.nih.gov/42017875/)
- [Phase 2b Randomized Trial of the Oral PCSK9 Inhibitor MK-0616 — J Am Coll Cardiol, 2023](https://pubmed.ncbi.nlm.nih.gov/36889610/)
- [Orally Bioavailable Macrocyclic Peptide That Inhibits Binding of PCSK9 to the Low Density Lipoprotein Receptor — Circulation, 2023](https://pubmed.ncbi.nlm.nih.gov/37125593/)
- [NCT06008756 — CORALreef Outcomes cardiovascular outcomes trial](https://clinicaltrials.gov/study/NCT06008756)

Note: Dose figures are left out of this Markdown version. See the cited sources.