Peptide LibraryEnlicitide
Also known as: Lipfendra, Enlicitide decanoate, MK-0616
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.
For research use only.
Key Facts
- CAS
- 2861205-06-1
- Molecular Weight (MW)
- 1722.12 g/mol
- Half-life
- Effective half-life about 14 hours; terminal half-life about 244 hours
- FDA status
- Approved
- Evidence level
- FDA Approved
- Human dose established
- Yes
- Administration Route
- Oral
- Frequency
- Once daily
- Last updated
- Oct 30, 2026
- Reviewed
- Oct 30, 2026
- Targets
- PCSK9
Research summary
FDA-approved oral macrocyclic peptide (Lipfendra, July 2026) that blocks PCSK9 to lower LDL cholesterol in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia.
Research evidence
- Regulatory review (FDA label)1 reviewed source
- Controlled human trials5 reviewed sources
- Early or uncontrolled human studies1 reviewed source
- Lab & animal studies1 reviewed source
How it works
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.
Peptide Library's Enlicitide profile summarises 5 cited studies listed in the Science section, the compound's regulatory status, and research-protocol parameters reported for it. It is a research reference, not medical advice.
Enlicitide dosage evidence
Enlicitide has an FDA-approved human dosage. As Lipfendra, approved in July 2026, it is one 20 mg tablet by mouth once daily on an empty stomach, for adults with high LDL cholesterol, including heterozygous familial hypercholesterolemia. It is taken in the morning with water, black coffee or plain tea, at least 30 minutes before food.
| Human dosing established | Yes |
|---|---|
| Studied dose range | 20 mg by mouth once daily |
| Route | Oral |
| Frequency | Once daily |
| Duration studied | Continuous |
| Titration | None. The label has a single 20 mg dose. LDL cholesterol can be measured as early as 4 weeks after starting. |
| Half-life | Effective half-life about 14 hours; terminal half-life about 244 hours |
| Evidence level | FDA Approved |
| Last reviewed | 2026-10-30 |
Research-reported dosing
Doses as studied, one row per regimen. Different trials used different regimens; they are listed separately rather than averaged.
| Study / context | Population | Dose | Route | Frequency | Duration | Outcome studied | Source |
|---|---|---|---|---|---|---|---|
| FDA label — LipfendraFDA-approved label · FDA prescribing information | Adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia, as an adjunct to diet and exercise | 20 mg | Oral tablet, swallowed whole on an empty stomach | Once daily, in the morning | Continuous | Reduction of LDL cholesterol | LIPFENDRA (enlicitide) tablets — FDA prescribing information, DailyMed |
| Navar et al., 2026 — CORALreef Lipids, phase 3Clinical trial · Randomised, double-blind, placebo-controlled phase 3 | 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) | 20 mg | Oral | Once daily | 52 weeks | LDL cholesterol changed by -57.1% at week 24 versus +3.0% on placebo | Navar AM et al. A Placebo-Controlled Trial of the Oral PCSK9 Inhibitor Enlicitide. N Engl J Med. 2026. |
| Ballantyne et al., 2026 — CORALreef HeFH, phase 3Clinical trial · Randomised, placebo-controlled phase 3 | Adults with heterozygous familial hypercholesterolemia on a moderate- or high-intensity statin (202 on enlicitide, 101 on placebo) | 20 mg | Oral | Once daily | 52 weeks | LDL cholesterol changed by -58.2% at week 24 versus +2.6% on placebo | Ballantyne CM et al. Efficacy and Safety of Oral PCSK9 Inhibitor Enlicitide in Adults With Heterozygous Familial Hypercholesterolemia: A Randomized Clinical Trial. JAMA. 2026. |
| Catapano et al., 2026 — CORALreef AddOn, phase 3Clinical trial · Randomised, double-blind, active-comparator phase 3 | Statin-treated adults needing further LDL lowering (101 on enlicitide, 200 on bempedoic acid, ezetimibe or both) | 20 mg | Oral | Once daily | 56 days | LDL cholesterol changed by -64.6% versus -6.3% with bempedoic acid, -27.8% with ezetimibe and -36.5% with both | Catapano AL et al. Oral PCSK9 Inhibitor Enlicitide Versus Oral Nonstatin Therapies: A Phase 3 Randomized Clinical Trial. J Am Coll Cardiol. 2026. |
| Ballantyne et al., 2023 — phase 2b dose-ranging trialClinical trial · Randomised, double-blind, placebo-controlled phase 2b | Adults with hypercholesterolemia across a wide range of cardiovascular risk (n=381) | 6, 12, 18 or 30 mg | Oral | Once daily | 8 weeks | Placebo-adjusted LDL cholesterol change of -41.2% (6 mg), -55.7% (12 mg), -59.1% (18 mg) and -60.9% (30 mg) | Ballantyne CM et al. Phase 2b Randomized Trial of the Oral PCSK9 Inhibitor MK-0616. J Am Coll Cardiol. 2023. |
| Johns et al., 2023 — first phase 1 studiesClinical trial · Phase 1 studies | Healthy adults (single rising doses) and participants on statins (multiple doses) | Single rising doses; 20 mg once daily in the multiple-dose study the abstract reports | Oral | — | 14 days (multiple-dose study) | Free PCSK9 fell by more than 93%; LDL cholesterol fell by up to 61% after 14 days of 20 mg | Johns DG et al. Orally Bioavailable Macrocyclic Peptide That Inhibits Binding of PCSK9 to the Low Density Lipoprotein Receptor. Circulation. 2023. |
| NCT06008756 — CORALreef Outcomes, ongoingClinical trial · Randomised, placebo-controlled phase 3 outcomes trial | Adults at high cardiovascular risk (estimated enrollment 14,550) | 20 mg | Oral | Once daily | — | Major cardiovascular events; no results yet (estimated completion 2031) | NCT06008756 — Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor) Cardiovascular Outcomes Study (CORALreef Outcomes) |
Preclinical and analog research
Not human dosing evidence. Listed for completeness and never extrapolated to a human dose.
| Study / context | Population | Dose | Route | Frequency | Duration | Outcome studied | Source |
|---|---|---|---|---|---|---|---|
| Preclinical — animal reproduction studiesPreclinical · Animal toxicology reported in the FDA label | Pregnant rats and rabbits | Up to 10 mg/kg/day in rats and 3 mg/kg/day in rabbits; not convertible to a human dose | Subcutaneous | Once daily | — | No adverse embryofetal or maternal effects at these doses, but enlicitide crossed the placenta in rats | LIPFENDRA (enlicitide) tablets — FDA prescribing information, section 8.1, DailyMed |
Where sources disagree
- The placebo-adjusted LDL reduction at week 24 is 56% in the primary analysis (label and NEJM). The label also gives 60% from a post hoc analysis that set LDL values of zero or below to missing, which is the figure some later papers quote.
- The label's cardiovascular statement is about LDL lowering with statins and monoclonal antibody PCSK9 inhibitors, not about enlicitide. Enlicitide's own outcomes trial, CORALreef Outcomes (NCT06008756), has not reported.
- Doses are given as enlicitide: one 20 mg tablet contains 22.21 mg of enlicitide decanoate. The registry entry for the phase 2b trial names enlicitide chloride, so its 6 to 30 mg arms are not the marketed salt.
- Food matters. Taken 30 minutes after a meal, exposure fell by about half (AUC 48%, Cmax 50%), and oral bioavailability is about 1%.
- Safety and effectiveness have not been established in children. A pediatric study is under way (NCT07058077).
Handling & administration
- Reconstitution Guide
- Not applicable: taken by mouth as a tablet
Sequence & molecular data
| Molecular formula | C92H129FN14O17 |
|---|---|
| Molecular weight | 1722.12 g/mol |
| CAS number | 2861205-06-1 |
| Half-life | Effective half-life about 14 hours; terminal half-life about 244 hours |
| Appearance | White to off-white, oval, film-coated tablets |
| Formulation | Oral tablet |
| PubChem CID | 172866837 |
| FDA UNII | PSR59MCX5M |
| ChEMBL | CHEMBL6068420 |
| KEGG | D13186 |
Identifiers link to the public PubChem, FDA Substance Registration (UNII), ChEMBL and DrugBank records for the same entity.
Science
Mechanism of Action
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. In the label, single doses of 10 mg or more cut free PCSK9 by more than 90% at peak drug levels. Each tablet contains sodium caprate, which helps a peptide this large get absorbed, and oral bioavailability is still only about 1%.
Origin
Synthetic macrocyclic peptide found by mRNA display screening and structure-based design at Merck (MSD).
Targets
Studies
- A Placebo-Controlled Trial of the Oral PCSK9 Inhibitor Enlicitide
- Efficacy and Safety of Oral PCSK9 Inhibitor Enlicitide in Adults With Heterozygous Familial Hypercholesterolemia: A Randomized Clinical Trial
- Oral PCSK9 Inhibitor Enlicitide Versus Oral Nonstatin Therapies: A Phase 3 Randomized Clinical Trial
- Phase 2b Randomized Trial of the Oral PCSK9 Inhibitor MK-0616
- Orally Bioavailable Macrocyclic Peptide That Inhibits Binding of PCSK9 to the Low Density Lipoprotein Receptor
Research statistics
45 PubMed publications · 15.8% human clinical research · 34 registered trials
Counts of published research through 2026-11-01, not evidence that it works. Publications by year, study types and trials · How publications are counted
Regulatory & research 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 |
|---|---|
| Research status | Approved product (see FDA status) |
| Availability | Prescription-Only |
| WADA (sport) | Unknown / Not Listed |
| Library classification | FDA-Approved |
How FDA approval, compounding and research-only status differ
Benefits
Enlicitide side effects
The effects below are drawn from Enlicitide's prescribing information, which lists the full adverse-reaction data.
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
Storage & stability
This compound is not supplied as a powder to be mixed, so the freeze-dried powder and reconstitution handling described for research peptides does not apply. Storage conditions are product-specific: follow the label or packaging of the product itself.
Enlicitide: 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 is the labeled dose of enlicitide?
The FDA label gives one 20 mg tablet by mouth once daily, on an empty stomach in the morning with water, black coffee or plain tea, at least 30 minutes before food. The tablet is swallowed whole. This is reference information, not medical advice.
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 is the half-life of enlicitide?
The label gives an effective half-life of about 14 hours and a terminal half-life of about 244 hours. Steady state is reached by about 7 days of daily dosing, with an accumulation ratio of 1.42.
Is enlicitide a peptide?
Yes. The FDA label describes it as a macrocyclic peptide. Peptides are usually broken down in the gut, so the tablet includes the absorption enhancer sodium caprate, and only about 1% of each dose is absorbed.
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, DailyMedExternal reference
- NDA 220848 approval letter — FDA, July 2026External reference
- A Placebo-Controlled Trial of the Oral PCSK9 Inhibitor Enlicitide — N Engl J Med, 2026External reference
- Efficacy and Safety of Oral PCSK9 Inhibitor Enlicitide in Adults With Heterozygous Familial Hypercholesterolemia — JAMA, 2026External reference
- Oral PCSK9 Inhibitor Enlicitide Versus Oral Nonstatin Therapies — J Am Coll Cardiol, 2026External reference
- Phase 2b Randomized Trial of the Oral PCSK9 Inhibitor MK-0616 — J Am Coll Cardiol, 2023External reference
- Orally Bioavailable Macrocyclic Peptide That Inhibits Binding of PCSK9 to the Low Density Lipoprotein Receptor — Circulation, 2023External reference
- NCT06008756 — CORALreef Outcomes cardiovascular outcomes trialExternal reference
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Compiled by Peptide Library Editorial · Reviewed Oct 30, 2026 · Updated Oct 30, 2026 · Version 1
This Enlicitide profile is compiled from published literature (5 cited studies linked above), public regulatory records and chemical registries. It describes what research reports; it is not medical advice, and nothing here is a dosing recommendation for humans. Peptide Library does not sell peptides. Editorial policy · How profiles are compiled · Report an error
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