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Prescription medication — not a dietary supplement
Inclisiran (Leqvio)is a prescription (or investigational) drug, not a supplement. It is included here for reference because people research and discuss it (often used off-label) — not as a recommendation. Take it only under a qualified clinician's supervision and only as prescribed; do not source it from grey-market vendors, where identity, purity, and dosing are unverified. The evidence below reflects its clinical trials.
What the evidence says
Most Inclisiran (Leqvio) studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.
Most evidence is from medium-quality meta-analyses and randomised trials published 2017–2023 with a typical study size of 501 participants.
Based on 7 studies · 2 meta-analyses · 3 RCTs · 8,203 total participants
Confidence
HighBy outcome
Inclisiran (Leqvio) has an evidence score of 4.1/10 — moderate evidence based on 7 indexed studies, including 2 meta-analyses. A small interfering RNA (siRNA) prescription drug (Leqvio) that silences PCSK9 in the liver, cutting LDL cholesterol ~50%. Distinctive for being dosed by subcutaneous injection only twice a year after the first doses — a major adherence advantage. LDL lowering is well established (ORION-9/-10/-11); cardiovascular-outcome benefit is NOT yet proven (ORION-4/VICTORION trials ongoing). Prescription drug, not a supplement. Representative study: PMID 33663735.
The commonly studied dose of Inclisiran (Leqvio) is 284 mg (300 mg inclisiran sodium) by subcutaneous injection administered by a healthcare professional on day 1, again at day 90 (month 3), then every 6 months thereafter. A prescription drug; this is the approved regimen, not a self-directed supplement protocol.. Individual needs vary — start at the lower end of the range and adjust based on how you respond.
Nicotinamide Riboside
Mostly mechanism / observationalA vitamin B3 precursor that reliably raises cellular NAD+ levels and is well tolerated — but human trials have so far shown mostly null or mixed results on the functional outcomes (muscle, metabolism, blood pressure, cognition) that elevation is meant to drive.
Alirocumab (Praluent)
Last reviewed June 2026 · evidence from 7 studies · how we score
This information is for educational purposes only. It is not a substitute for professional medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any supplement or medication.
Inclisiran (Leqvio) — PCSK9-targeting siRNA
A small interfering RNA (siRNA) prescription drug (Leqvio) that silences PCSK9 in the liver, cutting LDL cholesterol ~50%. Distinctive for being dosed by subcutaneous injection only twice a year after the first doses — a major adherence advantage. LDL lowering is well established (ORION-9/-10/-11); cardiovascular-outcome benefit is NOT yet proven (ORION-4/VICTORION trials ongoing). Prescription drug, not a supplement.
Inclisiran produces strong, durable ~50% LDL-cholesterol reductions across a well-conducted phase 3 program (ORION-9/-10/-11) with a twice-yearly dosing advantage, but cardiovascular-outcome benefit — actual reductions in heart attacks, strokes, and CV death — is not yet proven (ORION-4/VICTORION ongoing), so the overall evidence stays Moderate.
Inclisiran is a GalNAc-conjugated small interfering RNA (siRNA) that lowers LDL cholesterol by silencing PCSK9 messenger RNA inside hepatocytes.
The GalNAc sugar targets the molecule to liver cells, where the RNA-interference machinery degrades PCSK9 mRNA — so the liver makes less PCSK9, more LDL receptors stay on the cell surface, and more LDL is cleared from the blood.
It is a fundamentally different approach from statins (which block cholesterol synthesis) and from the PCSK9 monoclonal antibodies evolocumab and alirocumab (which mop up the PCSK9 protein after it is made); inclisiran shuts off production upstream.
The headline distinction is dosing: after an initial dose and one at day 90, inclisiran is given as a subcutaneous injection only twice a year (every 6 months), versus daily statins or fortnightly/monthly antibody injections — a potentially large real-world adherence advantage.
The pivotal phase 3 program (ORION-9 in heterozygous familial hypercholesterolemia, ORION-10 and ORION-11 in atherosclerotic cardiovascular disease / high risk) showed sustained placebo-corrected LDL-C reductions of roughly 48–52% maintained across the dosing interval, and the 4-year ORION-3 open-label extension showed the effect is durable with repeated dosing.
The honest limitation: those are LDL-lowering (surrogate) outcomes. Whether inclisiran actually reduces heart attacks, strokes, and cardiovascular death — the way statins and the PCSK9 antibodies have been shown to — is still unproven, with the cardiovascular-outcomes trials (ORION-4 and the VICTORION program) ongoing.
It is generally well tolerated; the most characteristic adverse effect is injection-site reactions (transient pain, redness, or a hardened area).
It is an expensive prescription drug administered by a clinician, not a supplement, and the score reflects strong, durable LDL-lowering evidence set against pending cardiovascular-outcome data and cost.
A small interfering RNA that engages the RNA-interference machinery to degrade PCSK9 messenger RNA in liver cells, so less PCSK9 protein is made.
A triantennary GalNAc sugar conjugate binds the asialoglycoprotein receptor, delivering the siRNA selectively into hepatocytes — enabling low, infrequent subcutaneous dosing.
Less PCSK9 means more LDL receptors recycle to the cell surface, clearing more LDL cholesterol from the blood — lowering LDL-C by roughly half.
How Inclisiran (Leqvio) works — from molecular targets to health outcomes. Click an edge to see supporting research.This visualization is in beta — pathways are being refined and expanded.
Tap node to isolate • Pinch to zoom • Tap edge for research
284 mg (300 mg inclisiran sodium) by subcutaneous injection administered by a healthcare professional on day 1, again at day 90 (month 3), then every 6 months thereafter. A prescription drug; this is the approved regimen, not a self-directed supplement protocol.
Loading: Initiation doses at day 1 and day 90 establish steady LDL lowering; maintenance is one injection every 6 months.
Can be taken without food
| Form | Type |
|---|---|
| 💊Prefilled subcutaneous injection (inclisiran 284 mg) | Recommended |
| 💊PCSK9 monoclonal antibodies (evolocumab / alirocumab) — proven CV-outcome benefit, more frequent dosing | Alternative |
| 💊Statins / ezetimibe — first-line, proven outcome benefit | Alternative |
Inclisiran's distinguishing feature is twice-yearly dosing; the antibodies and statins have proven cardiovascular-outcome data that inclisiran does not yet have.
Minimum: 13 weeks
Optimal: 52 weeks
Cycling: Not required
Note: Clinician-administered subcutaneous injection on day 1, day 90, then every 6 months; time of day and meals are irrelevant.
Dose-response data unavailable. The current published research for Inclisiran (Leqvio) does not provide sufficient dose-specific outcome data to generate reliable dose-response curves.
Refer to the Dosage & Timing section above for recommended dose ranges based on available evidence.
Placebo-corrected LDL-C reductions of roughly 48–52%, maintained across the dosing interval and durable over 4 years of repeated dosing.
After initial doses (day 1, day 90), it is injected only every 6 months — a potentially large real-world adherence advantage over daily or fortnightly therapies.
It lowers LDL strongly, but whether it reduces heart attacks, strokes, and CV death is still being tested (ORION-4 / VICTORION) — unlike statins and PCSK9 antibodies.
Generally well tolerated, but injection-site reactions (pain, redness, induration) are the characteristic side effect; it is an expensive clinician-administered drug.
Data are limited; avoid unless a clinician judges benefit to outweigh unknown risk.
Limited data in severe impairment; use under specialist supervision.
Be aware that inclisiran's outcome benefit is unproven; statins and PCSK9 antibodies have demonstrated event reduction.
Commonly and intentionally co-administered (additive LDL lowering); not a harmful interaction but combined lipid lowering should be clinician-monitored.
Redundant mechanism (both lower PCSK9 activity); combining is not standard and offers no established added benefit.
Tip: Usually transient and mild; rotate injection sites (abdomen, arm, thigh).
Tip: Generally self-limited; report persistent symptoms to your clinician.
Tip: Seek care for rash, swelling, or breathing difficulty after injection.
Timing is flexible for Inclisiran (Leqvio) — consistent daily use matters more than the time of day. A twice-yearly clinician-administered subcutaneous injection; timing relative to meals or time of day is not relevant.
Inclisiran (Leqvio) is generally safe at recommended doses, with a few precautions worth noting. The most commonly reported side effects are injection-site reaction (pain, redness, induration), arthralgia / limb pain, hypersensitivity reaction. Use caution if any of these apply to you: Known hypersensitivity to inclisiran or excipients; Not a substitute for a clinician's evaluation — prescription drug only.
A fully human monoclonal-antibody PCSK9 inhibitor (Praluent), injected under the skin every 2 weeks, that lowers LDL cholesterol by ~50–60%. In the ODYSSEY OUTCOMES trial of ~18,900 post-heart-attack patients it reduced major cardiovascular events and showed a possible all-cause mortality signal. Generally well tolerated; injection-site reactions and high cost/access are the main trade-offs. Prescription drug, not a supplement.