Side-by-side · Research reference

ACE-031vsRetatrutide

Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.

APhase 2HUMAN-REVIEWED10/44 cited

BPhase 2HUMAN-REVIEWED10/41 cited

ACE-031

ActRIIB-Fc Fusion · Phase 2 Halted

Phase 2Highest trial stage

2011Development halted

~58.4 kDaMolecular weightReichel 2025

SQ · Weekly dosing investigated

Retatrutide

Triple-receptor agonist · Phase 3

1–12 mgWeekly doseJastreboff 2023

24.2%Body-weight ↓Jastreboff 2023

~6 daysHalf-life (est)

SQ · Abdomen · Once weekly

01Mechanism of Action

Parameter

ACE-031

Retatrutide

Primary target

Myostatin, GDF11, activin A — TGF-β superfamily ligands

GLP-1R + GIPR + Glucagon receptor (triple agonism)Jastreboff 2023

Pathway

Soluble decoy receptor binds circulating myostatin/TGF-β ligands → prevents ActRIIB activation → SMAD2/3 pathway inhibition

Triple-receptor activation → ↑insulin (GLP-1+GIP), ↓gastric emptying, ↑lipid handling, ↑energy expenditure (glucagon component)Jastreboff 2023

Downstream effect

Disinhibition of myogenic signaling, increased skeletal muscle mass and strength

Maximal weight loss across class. Glucagon component drives lipolysis and energy expenditure beyond GLP-1+GIP aloneJastreboff 2023

Feedback intact?

—

Origin

Recombinant fusion protein: human ActRIIB extracellular domain + IgG1-Fc fragmentReichel 2025

Synthetic peptide engineered for balanced affinity at three incretin / glucagon receptorsJastreboff 2023

Antibody development

—

02Dosage Protocols

Parameter

ACE-031

Retatrutide

Clinical dosing

Weekly or biweekly SQ injections (exact doses undisclosed pre-halt)

Phase 2 DMD trial protocol not fully published.

—

Black market products

Variable purity; 12/14 tested products contained target protein plus contaminantsReichel 2025

SDS-PAGE revealed multiple protein bands; quality control absent.Reichel 2025

—

Evidence basis

Phase 2 trial discontinued — incomplete dataset

Phase 2 trial; Phase 3 ongoingJastreboff 2023

Half-life

Days to weeks (Fc-fusion typical kinetics)

IgG1-Fc domain confers extended circulation time.

~6 days (estimated from class)

Duration investigated

12–24 weeks (trial cut short)

—

Standard dose

—

12 mg / week (max efficacy)Jastreboff 2023

Phase 2 trial dose. Phase 3 dosing TBD.

Frequency

—

Once weekly

Titration schedule

—

2 mg → 4 mg → 8 mg → 12 mg over 16 weeks

Duration

—

Indefinite for chronic indication (presumed)

Reconstitution

—

Investigational; not commercially available

Timing

—

Any time of day

04Side Effects & Safety

Parameter

ACE-031

Retatrutide

Epistaxis (nosebleeds)

Significant incidence in Phase 2 DMD trial — primary safety signal

—

Telangiectasia

Dilated capillaries / spider veins observed

—

Vascular abnormalities

Mechanism: ActRIIB/ALK1 pathway disruption affects vascular homeostasis

—

Injection site reactions

Local erythema, induration (biologics class effect)

—

Antibody development

Potential for anti-drug antibodies (Fc-fusion proteins); incidence not reported

—

Black market contaminants

12/14 tested products contained multiple unidentified proteins alongside ACE-031Reichel 2025

—

GI symptoms

—

Nausea, vomiting, diarrhea (very common, dose-dependent)Jastreboff 2023

Heart rate

—

↑ resting HR (3–7 bpm at 12 mg)Jastreboff 2023

Glucose handling

—

Glycemic improvement; rare hyperglycemia from glucagon component

Pancreatitis risk

—

Class warning

Thyroid C-cell tumours

—

Class warning (presumed)

Pregnancy / OB

—

Avoid (insufficient data)

Absolute Contraindications

ACE-031

·History of vascular disorders (epistaxis, telangiectasia, HHT)
·Pregnancy (TGF-β pathway critical for fetal development)
·Active malignancy (myostatin inhibition may affect tumour growth)
·Use of non-pharmaceutical grade ACE-031 (contamination risk)Reichel 2025

Retatrutide

·MTC personal or family history (presumed class effect)
·Pregnancy / breastfeeding

Relative Contraindications

ACE-031

·Coagulation disorders or anticoagulant use (epistaxis risk)
·Hereditary hemorrhagic telangiectasia (HHT) family history
·Cardiovascular disease (vascular remodeling effects unknown)

Retatrutide

·Severe gastroparesis
·History of pancreatitis
·Severe cardiovascular disease (HR signal)

05Administration Protocol

Parameter

ACE-031

Retatrutide

1. Pharmaceutical status

ACE-031 is not FDA-approved or commercially available. Phase 2 development was discontinued in 2011 due to safety concerns. Any ACE-031 on the black market is unregulated research chemical.

Investigational peptide. Research vials reconstituted with bacteriostatic water per label.

2. Black market quality

12 of 14 tested black market ACE-031 products contained the target protein but also carried multiple unidentified protein contaminants detectable by SDS-PAGE. Two products contained no ACVR2B-immunoreactive material.Reichel 2025

SQ — abdomen, thigh, or upper arm. Rotate weekly.

3. Detection in sport

ACE-031 is prohibited under WADA S4.3 (Myostatin Inhibitors). Gel electrophoresis and Western blotting using ACVR2B-specific antibodies can detect the ~58.4 kDa protein in biological samples.Reichel 2025

Once weekly, same day.

4. Clinical trial route

Phase 2 protocol used subcutaneous injections at weekly or biweekly intervals. Exact dosing protocols remain unpublished.

Refrigerate 2–8 °C. Light-protected.

5. Needle

—

27–31G, 4–8 mm insulin syringe.