Enlicitide

LIPFENDRA

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Pronunciation: en-LI-si-tide

Enlicitide ballicule: receptor binding, kinetics and half-life diagram — Mechanism of action: Enlicitide ballicule

Enlicitide LIPFENDRA mascot mnemonic cartoon — Visual mnemonic: Enlicitide mascot
**“Endless tide, Lippy defender”**
Pesky K-9 → PCSK9, which targets LDL receptors for destruction
Pill → the first ORAL PCSK9 inhibitor (2026)

What it isOral macrocyclic peptide that blocks PCSK9–LDL-receptor binding (LIPFENDRA, 2026); hypercholesterolemia including HeFH.

Why this onePCSK9 blockade in a pill: placebo-adjusted LDL-C reductions of 56-59% at week 24, with very low CYP/transporter interaction potential.

What limits itThe catch is the empty stomach: food 30 minutes before cuts exposure roughly in half (AUC -48%); then 30 minutes of nothing else.

Enlicitide molecular structure (skeletal formula) — Molecular structure: Enlicitide

FDA-approved for

hypercholesterolemia incl. HeFH (2026)

FDA label

Read the full label on DailyMed ↗

FDA dosing	Population	Start	Target	Max
Hypercholesterolemia (incl. HeFH), adjunct to diet/exercise to reduce LDL-C	Adults	20 mg QD	20 mg QD	20 mg QD

Renal Undefined

Hepatic Undefined

LDL-C-lowering effect measurable as early as 4 weeks after initiation; assess LDL-C when clinically appropriate

Instructions

Take on an empty stomach in the morning with water, black coffee, or plain tea
Swallow tablet whole; do not split, crush, or chew
Wait ≥30 min after dose before eating or drinking anything other than water, black coffee, or plain tea
Missed dose: take ASAP ≥30 min before next food/drink (other than water/black coffee/plain tea); never 2 doses same day
Can be taken with other medications

Available strengths

tab 20 mg

Cautions

May cause fetal harm based on mechanism (lowers cholesterol-derived substances); discontinue when pregnancy recognized unless benefit outweighs risk

Adverse reactions

HeFH trial: diarrhea (7% vs 2% placebo), dizziness (9% vs 4%)
General hypercholesterolemia trial: adverse reaction rates similar to placebo

Pregnancy Discontinue when pregnancy recognized unless benefit outweighs fetal risk; may cause fetal harm by mechanism of action; no adverse embryofetal effects in animals up to 51–58× human exposure

Lactation No human data on milk presence, infant effects, or milk production; weigh benefits of breastfeeding vs maternal need

Cost

Enlicitide (LIPFENDRA)

Strength		#/mo	generic $/mo	CostPlus
20 mg	tab	30 qd		not offered

NADAC is a voluntary CMS survey of what retail community pharmacies pay for the drugs they stock. Enlicitide is dispensed outside retail pharmacies, so it rarely appears on surveyed invoices.

NO BOXED WARNINGS

Classes and tags

Clinical profile

Therapeutic safety burden1 / 4

Overdose danger1 / 4

Weight-gain liability0 / 4

Sedation liability0 / 4

QT / Torsades0 / 4

Direct muscarinic antagonism0 / 4

Embryofetal risk2 / 4

Legacy pregnancy categoryN/A (post-2015 labeling)

Defining liabilityFood-dependent absorption; limited long-term experience

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Memory aids: interaction avatars

empty stomach — food ↓AUC ~48%

Open Enlicitide in the interactive console ↗