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Enlicitide for Health & Longevity

Created on 11/08/2026 – Quick Reference based on Evidence Review created using AI4L / Opus 5.5 – Audit

Enlicitide is a prescription oral medication, the first tablet to block a liver protein that destroys cholesterol-clearing receptors, used to lower plaque-forming cholesterol particles over decades. In year-long trials it produced large, lasting falls on top of standard cholesterol drugs. Whether it prevents heart attacks or strokes is not yet shown. Side effects were few. Its effect depends on being taken on an empty stomach. The manufacturer funded every trial. (Full Review)

Protocol

Standard dose
20 mg once daily
One tablet; the approved dose and the pivotal phase 3 trial dose
Time of day
Morning, empty stomach
Swallowed whole with water, black coffee or plain tea; no food for 30 minutes
Single vs split dose
A single daily dose
Not split, crushed or chewed; a missed dose is taken that day before food, never two doses in one day
Time to effect
LDL-C reduction
Week 8
Reductions of 41–61% versus placebo in the phase 2b trial
Sustained LDL-C lowering
Through 52 weeks
The placebo-adjusted reduction was smaller at week 52
Free PCSK9
Within hours
Over 90% lower within 0.5–1 hour at doses of 10 mg or more

Benefits

Contraindications
  • Pregnancy
  • Children under 18
  • Severe liver impairment (Child-Pugh Class C)
  • Breastfeeding
  • Homozygous FH with no functional LDLR
    •
Key Interactions
  • Food and caloric drinks
    •
Theoretical (inferred from mechanism)
  • Other PCSK9-targeted drugs (evolocumab, inclisiran)
  • Bile-acid sequestrants (cholestyramine, colesevelam)
  • Calorie-containing supplements (fish oil, protein shakes)
  • Over-the-counter orlistat or stimulant laxatives (bisacodyl, senna)
  • LDL-lowering supplements (red yeast rice, berberine)
  • LDL apheresis
    •

Risk & Side Effects

  • High:
  • Medium:
  • Low: Diarrhea; dizziness; new-onset diabetes
    •
  • Speculative: Fetal harm; gut-lining effects of sodium caprate; effects of very low LDL-C on cognition
    •

Monitoring

Marker Target Why
LDL-C <55 mg/dL very-high-risk, <70 mg/dL high-risk Main efficacy marker
ApoB <65 mg/dL very-high-risk, <80 mg/dL high-risk Counts plaque-forming particles
Non-HDL-C <85 mg/dL very-high-risk, <100 mg/dL high-risk Captures all plaque-forming cholesterol
Lp(a) No established target; track change from own baseline Expected to change modestly
HbA1c <5.7% Safety check for the genetic diabetes signal
Fasting glucose Not specified in the ER Paired with HbA1c; screens for the diabetes caution
Pregnancy status Not specified in the ER Baseline check for women who could become pregnant

Cadence: Baseline lipid panel, one-time Lp(a), HbA1c and fasting glucose; lipid panel 4–12 weeks after starting, then every 6–12 months once stable; HbA1c every 6–12 months

Qualitative Assessment

  • Stool frequency and consistency, especially in the first weeks
  • Episodes of dizziness or lightheadedness
  • Consistency of fasting morning dosing (missed or food-adjacent doses)
  • Energy and exercise tolerance compared with any prior statin experience
Not medical advice. Educational distillation of a single evidence review. Confirm any decision with a qualified clinician, especially in the presence of prescription drugs or chronic conditions.