The Peptide Desk The Peptide Desk

This information is for research and educational purposes only. No medical recommendations. Products are not approved for human use. For health questions, consult a doctor.

Lexicon
Lexicon

Bempedoic acid (Nexletol)

The cholesterol agent that never gets activated in muscle - the option after statin muscle pain.

3 min read 7 sources

To the sources
Long, stretched molecule chain of glossy blue and white spheres floats above a white podium with a glowing rim in a bright lab, symbolic image for bempedoic acid
Compound approved · since 2020

Summary

At a glance

Sources checked on 26 Oct 2026

CLEAR Outcomes
13,970 participants

statin intolerance and high cardiovascular risk, median 40.6 months1

Major cardiovascular events
−13 %

11.7 versus 13.3 percent with placebo (hazard ratio 0.87)1

LDL without a statin (CLEAR Serenity)
−21.4 %

against placebo after 12 weeks, 345 people with statin intolerance4

Half-life
~21 hours

at steady state, spread ±11 hours5

  • Bempedoic acid inhibits ATP citrate lyase, an enzyme one step before the target of statins. The liver makes less cholesterol and pulls more LDL out of the blood.75
  • It only becomes active after activation by the enzyme ACSVL1. That enzyme sits mainly in the liver and is absent from skeletal muscle.54
  • On top of a statin LDL fell by 17 to 18 percent against placebo, in statin intolerance without a statin by 21 percent.234
  • In CLEAR Outcomes with almost 14,000 people major cardiovascular events fell by 13 percent. Gout, gallstones, uric acid and tendon ruptures occurred more often.15
  • According to ChEMBL bempedoic acid has been approved since 2020. Everything here is the state of research, not a recommendation.7
Profile

Updated July 2026

Class
ATP citrate lyase inhibitor

prodrug

Use
Oral

once daily, a single dose step

LDL reduction
20 to 25 percent as monotherapy
Distinctive
Activating enzyme is absent from skeletal muscle
Watch for
Raises uric acid

slightly increased tendon rupture risk

Contents 12 sections
  1. At a glance
  2. What is bempedoic acid?
  3. How it works
  4. Use and dosing
  5. What the research shows
  6. Research status
  7. Side effects
  8. Storage
  9. Related compounds
  10. FAQ
  11. Glossary
  12. Sources

What is bempedoic acid?

Bempedoic acid lowers LDL through the same metabolic pathway as a statin but acts one step earlier. Statins inhibit HMG-CoA reductase, bempedoic acid inhibits ATP citrate lyase, which sits further upstream in cholesterol synthesis. The result is the same: the liver cell puts more LDL receptors on its surface and pulls more LDL out of the blood.

The actual trick lies elsewhere. Bempedoic acid is a prodrug and first has to be activated by an enzyme called ACSVL1. That enzyme sits in the liver and is absent from skeletal muscle. So the active drug never even forms in muscle.

This information is for research and educational purposes only. No medical advice.

Comparison

Three paths to less LDL

Bempedoic acid, statins and ezetimibe act at different points, as stated in the TPD lexicon. Tap a card to open its entry.

ATP citrate lyase inhibitor Bempedoic acid (Nexletol) ACLY
Statin Atorvastatin (Lipitor) HMGCR Statin Rosuvastatin (Crestor) HMGCR Gut uptake inhibitor Ezetimibe (Ezetrol, Zetia) NPC1L1

Simplified: bempedoic acid acts one step before statins in cholesterol production, ezetimibe slows uptake in the gut. 75

How it works

Statin-associated muscle complaints are the most common reason people stop a cholesterol agent. That is exactly where the design of bempedoic acid starts: no activating enzyme in muscle, so no active drug in muscle, so theoretically no muscle burden. The registration trials confirmed this, with muscle complaint rates sitting at placebo level.

As monotherapy it lowers LDL by roughly 20 to 25 percent, meaning less than a mid-range statin. Combined with ezetimibe another 20 percent or so is added, which is why the two also exist as a fixed combination.

Where it acts

Where bempedoic acid acted in studies

Tap a point or a card. Colour = ATP citrate lyase, grey = observed in studies.

  1. Liver

    Activation by ACSVL1, less cholesterol production, more LDL receptors5

    ACLY
  2. Blood lipids

    LDL lowered by 17 to 21 percentage points against placebo4

    Observed in trials
  3. Heart

    Heart attacks 3.7 versus 4.8 percent1

    Observed in trials
  4. Muscle

    No activating enzyme, muscle pain not more common than on placebo4

    Observed in trials
  5. Kidney

    Inhibits a uric acid transporter, uric acid and creatinine rise slightly5

    Observed in trials
  6. Tendons

    Tendon ruptures 1.2 versus 0.9 percent (Outcomes)5

    Observed in trials

Targets in the ChEMBL database7

Compound CHEMBL3545313: one recorded mechanism, Inhibitor, direct binding.

ATP citrate lyase
Gene
ACLY
UniProt
P53396
ChEMBL
CHEMBL3720
Action
Inhibitor, direct binding
Two glass chambers side by side: on the left a glowing blue liver cell with blue molecule chains, on the right reddish muscle fibres without molecules
Bempedoic acid is activated in the liver, not in skeletal muscle. Symbolic image.

Use and dosing

Dosing

Dosing, titration and syringe

Loading the dosing information …

  • Getting started and stepping up, drawn as a staircase
  • Units on the U-100 syringe for every step
  • How long one vial lasts
White folding box with the TPD logo next to a blister of ten round white tablets, two loose tablets in front on a bright lab bench
Tablets in a blister. Symbolic image.

What the research shows

CLEAR Outcomes (NEJM 2023) is the decisive trial, because it is the only one that tested hard endpoints. Almost 14,000 patients with statin intolerance and cardiovascular risk received bempedoic acid or placebo. The combined endpoint of heart attack, stroke, revascularisation and cardiovascular death fell by 13 percent. That is a real but moderate effect and matches the moderate LDL reduction.

CLEAR Harmony (NEJM 2019) tested safety over 52 weeks in over 2,200 patients and showed an LDL reduction of around 18 percent on top of statin therapy. CLEAR Wisdom (JAMA 2019) confirmed roughly 17 percent additional reduction at maximally tolerated statin dose. CLEAR Serenity (J Am Heart Assoc 2019) specifically examined statin-intolerant patients and arrived at around 21 percent.

The trials are consistent with each other, which speaks for the substance. What is missing is long-term data across many years of the kind that exists for statins.

Study results

What the trials measured

Interactive: switch tabs, tap points, show or hide arms. Arms are named relative to each other, no dosing advice.

LDL reduction against placebo2341

Difference from placebo in percentage points, after 12 weeks (Outcomes after 6 months)

CLEAR Harmony2 on top of a statin, 2,230 people
Bempedoic acid -18.1 pp
CLEAR Wisdom3 on top of a statin, 779 people
Bempedoic acid -17.4 pp
CLEAR Serenity4 statin intolerance, 345 people
Bempedoic acid -21.4 pp
CLEAR Outcomes1 statin intolerance, 13,970 people
Bempedoic acid -21.1 pp

Values from the abstracts. With a statin in the background the extra effect is smaller than without.

Events over a median of 40.6 months1

Share of participants, 6,992 on bempedoic acid, 6,978 on placebo

Primary endpoint (four events)1
Placebo 13.3%
Bempedoic acid 11.7%
Heart attack1
Placebo 4.8%
Bempedoic acid 3.7%
Revascularisation1
Placebo 7.6%
Bempedoic acid 6.2%

Bempedoic acid had no significant effect on stroke, cardiovascular death and all-cause mortality.

Glass liver model and a branched glass vessel on a white surface, surrounded by Petri dishes with light blue samples and pipettes
Four large trials with more than 17,000 people combined. Symbolic image.

Research status

Where the research stands

Bempedoic acid has been approved since 2020. On ClinicalTrials.gov 54 trials list bempedoic acid among their interventions, 16 of them in phase 3. Shown are the four registration and outcome trials from this entry. As of 26 Oct 2026. 6

  1. Preclinical Prodrug, activated by ACSVL1 mainly in the liver
  2. Phase 1 no registered trial
  3. Phase 2 no registered trial
  4. Phase 3 4 trials, 4 completed
  5. Approval since 2020
17,324 participants in phase 3 Approved: ChEMBL lists bempedoic acid with phase 4 as the highest phase and first approval in 2020.7
Show all 4 phase 3 trials on a timelineHide timeline 4 completed 0 running 4 with results
Phase 3

Bar: start to primary endpoint (planned for running trials). Green = completed, blue = progress until 26 Oct 2026.

Side effects

  • Raised uric acid: the most relevant side effect. Anyone prone to gout or already running high values should keep an eye on it. Gout attacks occurred more often than under placebo in the trials.
  • Tendon rupture: a slightly elevated risk is documented. For anyone training hard this matters more than for the average patient and deserves an honest mention.
  • Liver values: small rises possible.
  • Kidney values: a slight creatinine rise is described, usually without disease significance.

Tolerability

Side effects compared with placebo

Out of 100 participants, how many had the side effect, on bempedoic acid and on placebo.

8 of 100 Placebo
16 of 100 Bempedoic acid
Event PlaceboBempedoic acid
Raised uric acid as an adverse event (Outcomes)5 8%16%
Gout1 2%3%
Gallstones1 1%2%
Tendon rupture (Outcomes)5 1%1%
Muscle pain (Serenity)4 7%5%

Muscle pain occurred less often on bempedoic acid than on placebo in statin-intolerant people. In CLEAR Harmony 10.9 instead of 7.1 percent stopped because of side effects.42

Storage

Store dry, at room temperature and protected from light. Keep out of reach of children.

Three white tablet bottles on a bright shelf next to a folded light blue towel
Dry, at room temperature and away from light. Symbolic image.

Related

Related compounds

A different path: all in the TPD lexicon.

Bempedoic acid (Nexletol)
Atorvastatin (Lipitor) Statin, inhibits one step later in the same pathway Rosuvastatin (Crestor) Statin, inhibits one step later in the same pathway Ezetimibe (Ezetrol, Zetia) Slows cholesterol uptake in the gut, often used together Metformin (Glucophage) Different path, blood sugar instead of blood lipids

FAQ

Common questions about Bempedoic acid (Nexletol)

Short answers, each backed by the sources below.

How is bempedoic acid different from a statin?

Both slow cholesterol production in the liver, but bempedoic acid acts one step earlier at ATP citrate lyase. It is also a prodrug: only the enzyme ACSVL1 makes it active. That enzyme is found mainly in the liver, not in skeletal muscle.54

Is bempedoic acid approved?

Yes. ChEMBL lists bempedoic acid as an approved compound with first approval in 2020. ClinicalTrials.gov lists 54 trials, 16 of them in phase 3 (as of 26 October 2026). Everything here is the state of research, not a recommendation.76

How much does it lower LDL?

On top of a statin by 18.1 (Harmony) and 17.4 percentage points (Wisdom) more than placebo. In statin intolerance without a statin it was 21.4 percentage points (Serenity). All trials used only one dose, 180 mg once daily.234

What did CLEAR Outcomes show?

13,970 people with statin intolerance were followed for a median of 40.6 months. The primary endpoint of cardiovascular death, heart attack, stroke and revascularisation occurred in 11.7 instead of 13.3 percent. Heart attacks and revascularisations became less common, stroke and mortality did not change significantly.1

Why does uric acid rise?

Bempedoic acid inhibits a transporter in the kidney (OAT2) that excretes uric acid. In CLEAR Outcomes 16.4 instead of 8.2 percent had raised uric acid as an adverse event, gout occurred in 3.1 instead of 2.1 percent. The rise usually came within the first four weeks and went back after stopping.51

What about tendon ruptures?

The label warns about it. In the lipid trials tendons at the shoulder, biceps or Achilles ruptured in 0.5 percent, on placebo in no one, in CLEAR Outcomes in 1.2 versus 0.9 percent. People over 60, on corticosteroids or fluoroquinolones, with kidney failure or earlier tendon problems are affected more often.5

Glossary

Terms explained briefly

Dotted words in the text open these explanations directly.

ACSVL1
Enzyme that activates bempedoic acid. It is found mainly in the liver, not in skeletal muscle.
ATP citrate lyase
Enzyme that supplies building blocks for fat and cholesterol production. Bempedoic acid inhibits it.
Creatinine
Breakdown product from muscle that the kidney excretes. The blood level indicates kidney function.
Ezetimibe
A compound that slows the uptake of cholesterol in the gut.
HMG-CoA reductase
Enzyme in the liver targeted by statins. It lies in the pathway after ATP citrate lyase.
LDL receptor
Docking site on the liver cell through which LDL is taken up from the blood.
Placebo
Dummy preparation without active substance. Comparing against it shows what is due to the substance itself.
Prodrug
A precursor of a compound that is only converted into its active form in the body.
Revascularisation
A procedure that reopens a narrowed heart vessel, for example with a stent or bypass.
Skeletal muscle
The voluntarily moved muscles of the arms, legs and trunk.
Statin
A compound that inhibits HMG-CoA reductase, the key enzyme of cholesterol production.
Uric acid
Breakdown product in the blood. Too much of it can crystallise in joints and trigger gout.

Evidence

Sources

Show all 7 sourcesHide sources 4 Studies1 Trial registry2 Database checked 26 Oct 2026

Studies

  1. CLEAR Outcomes: cardiovascular events in statin intolerance

    Nissen et al., New England Journal of Medicine, 2023

    DOI 10.1056/NEJMoa2215024 PMID 36876740 NCT02993406
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  2. CLEAR Harmony: safety and efficacy over 52 weeks

    Ray et al., New England Journal of Medicine, 2019

    DOI 10.1056/NEJMoa1803917 PMID 30865796 NCT02666664
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  3. CLEAR Wisdom: on top of the highest tolerated statin dose

    Goldberg et al., JAMA, 2019

    DOI 10.1001/jama.2019.16585 PMID 31714986 NCT02991118
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  4. CLEAR Serenity: bempedoic acid in statin intolerance

    Laufs et al., Journal of the American Heart Association, 2019

    DOI 10.1161/JAHA.118.011662 PMID 30922146 NCT02988115
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed

Trial registry

  1. Trials on bempedoic acid on ClinicalTrials.gov

    ClinicalTrials.gov, U.S. National Library of Medicine

    Checked 26 Oct 2026 via ClinicalTrials.gov API v2

Database

  1. US prescribing information for bempedoic acid

    DailyMed, U.S. National Library of Medicine (Stand 25.06.2026)

    Checked 26 Oct 2026 via DailyMed, openFDA
  2. Mechanism and approval in ChEMBL

    ChEMBL, EMBL-EBI (CHEMBL3545313)

    Checked 26 Oct 2026 via ChEMBL