Evidence review: Open Peptide Project (verified against primary PubMed, ClinicalTrials.gov & FDA records) · Last checked 2026-10-27. ← Back to Evidence Library

Enlicitide (Lipfendra, MK-0616): what the evidence says

Name: Enlicitide (Lipfendra, MK-0616)
Published: 2026-10-27

At a glance

What it is: an oral macrocyclic peptide that blocks PCSK9, the same target as the injectable antibodies evolocumab and alirocumab. FDA-approved as Lipfendra (Merck Sharp & Dohme) in Jul 2026 to lower LDL cholesterol in adults with hypercholesterolemia, including the inherited form (HeFH). ^{R1, R2, R3}

What the evidence says: Human in CORALreef Lipids (about 2,900 adults), enlicitide lowered LDL cholesterol by about 56 percentage points more than placebo at 24 weeks. ^{R4, R2} Trials showing fewer heart attacks or strokes have not reported yet.

Biggest risks: most common side effects in the label were diarrhea and dizziness; adverse events overall were similar to placebo in the phase 3 trial. ^{R2, R4}

Rating


Human Human evidence	Strong: phase 3 RCTs (n = 2,909; n = 301) ^{R4, R5}
Animal Animal / lab evidence	Not reviewed
Regulatory	FDA-approved ^R1 · not on FDA's 503A or 503B bulk-substance category lists and not on FDA's compounding safety-risk page ^{R6, R7, R8} · not named by WADA ^R9
Established human dose	Yes, label dose (see Study details)

Evidence verdict: High LDL cholesterol: Strong (phase 3 RCTs) · Heart attack and stroke prevention: No outcomes data yet

This page reports what studies used. It is not dosing advice.

Legend: HUMAN data · ANIMAL / LAB data · UNKNOWN · UNVERIFIED: not yet confirmed against a primary source

About the evidence: large sponsor RCTs on a lab endpoint (LDL); cardiovascular outcome results are not yet available.

What is it?

Related pages: semaglutide, rusfertide.

Does it work?

Human CORALreef Lipids: LDL −55.8 percentage points vs placebo at week 24. ^{R4, R10}
Human CORALreef AddOn: LDL −64.6% vs −27.8% (ezetimibe), −6.3% (bempedoic acid), −36.5% (both). ^{R5, R11}
Human Phase 2b: LDL down 41% to 61% across doses. ^{R3, R12}
⚪ Heart attack and stroke: no outcomes data yet.

Is it safe?

Most common adverse reactions: diarrhea, dizziness. ^R2
Human Adverse events similar to placebo in CORALreef Lipids. ^R4

Gray-market vials: extra risks

A gray-market vial has no quality control and no guarantee of identity, strength or sterility. We test retail vials blind under the Open Peptide Standard; see /tests/. A passing test covers one batch on one date and does not mean the compound is safe.

Is it legal?

US: FDA-approved, prescription (Lipfendra, approved Jul 15, 2026). ^R1
Compounding: not on FDA's 503A or 503B bulk-substance category lists and not on FDA's compounding safety-risk page. ^{R6, R7, R8}
Sport: not named on WADA's 2026 Prohibited List. ^R9

Study details

These are amounts researchers used, not recommendations.

Study	People / model	Route	Amount used	Follow-up	Reported	Citation
Phase 2b 2023	381 adults, hypercholesterolemia	Oral	Range, per study	8 weeks	LDL −41% to −61% vs placebo	PMID 36889610
CORALreef Lipids 2026	2,909 adults at high cardiovascular risk	Oral	Per label	24 weeks (52 total)	LDL −55.8 points vs placebo	PMID 41879224
CORALreef AddOn 2026	301 adults on statins	Oral	Per label	8 weeks	LDL −64.6% vs comparators	PMID 42017875

Full reference list (PubMed, CT.gov, FDA and WADA checked Oct 27, 2026)

^R1 Drugs@FDA, Lipfendra (enlicitide), application NDA220848 (openFDA drugsfda record checked Oct 27, 2026). https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=NDA220848
^R2 Lipfendra prescribing information, label published Jul 27, 2026 (DailyMed, checked Oct 27, 2026). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=100ec543-fbd0-44fc-b740-db9cdff39145
^R3 Ballantyne CM, et al. J Am Coll Cardiol. 2023. PMID 36889610
^R4 Navar AM, et al. N Engl J Med. 2026. PMID 41879224
^R5 Catapano AL, et al. J Am Coll Cardiol. 2026. PMID 42017875
^R6 FDA, 503A bulk drug substances categories list (updated May 14, 2026). https://www.fda.gov/media/94155/download
^R7 FDA, 503B bulk drug substances categories list (updated Mar 21, 2025). https://www.fda.gov/media/94164/download
^R8 FDA, Certain bulk drug substances for use in compounding that may present significant safety risks (content current Apr 22, 2026). https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks
^R9 WADA. The 2026 Prohibited List, full list checked; compound not named. https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf
^R10 ClinicalTrials.gov NCT05952856, CORALreef Lipids, phase 3 (CT.gov API v2, checked Oct 27, 2026). https://clinicaltrials.gov/study/NCT05952856
^R11 ClinicalTrials.gov NCT06450366, CORALreef AddOn, phase 3, completed (CT.gov API v2, checked Oct 27, 2026). https://clinicaltrials.gov/study/NCT06450366
^R12 ClinicalTrials.gov NCT05261126, phase 2b, completed, 381 enrolled (CT.gov API v2, checked Oct 27, 2026). https://clinicaltrials.gov/study/NCT05261126

Disclaimer

This page is for education and harm reduction, not medical advice or a recommendation to use Enlicitide (Lipfendra, MK-0616). This is a prescription medicine. Use it only under the care of a licensed clinician; do not buy it from research-chemical or gray-market sellers. Report problems to FDA MedWatch (https://www.fda.gov/safety/medwatch).