Side-by-side · Research reference

ACE-031vsLiraglutide

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

BFDA-ApprovedFlagship14/45 cited

ACE-031

ActRIIB-Fc Fusion · Phase 2 Halted

Phase 2Highest trial stage

2011Development halted

~58.4 kDaMolecular weightReichel 2025

SQ · Weekly dosing investigated

Liraglutide

Daily GLP-1 RA · FDA-Approved

0.6–3.0 mgDaily doseSAXENDA (liraglutide) injectio 2014

5–10%Body-weight ↓SAXENDA (liraglutide) injectio 2014

~13 hrHalf-lifeSAXENDA (liraglutide) injectio 2014

SQ · Abdomen / thigh / arm · Once daily

01Mechanism of Action

Parameter

ACE-031

Liraglutide

Primary target

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

GLP-1 receptor (GLP-1R)SAXENDA (liraglutide) injectio 2014

Pathway

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

GLP-1R agonism → ↑glucose-dependent insulin, ↓glucagon, ↓gastric emptying, ↓appetiteSAXENDA (liraglutide) injectio 2014 Marso 2016

Downstream effect

Disinhibition of myogenic signaling, increased skeletal muscle mass and strength

Glycemic improvement, modest body-weight reduction, cardiovascular event reduction in high-risk T2DMarso 2016

Feedback intact?

—

Glucose-dependent insulin release preserves physiological feedback

Origin

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

Modified GLP-1(7-37) with Lys26 substitution (Arg34) and C-16 palmitoyl-glutamate acylation for albumin bindingSAXENDA (liraglutide) injectio 2014

Antibody development

—

02Dosage Protocols

Parameter

ACE-031

Liraglutide

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

FDA-approved · Phase 3 RCTs (LEADER, SCALE)Marso 2016 SAXENDA (liraglutide) injectio 2014

Half-life

Days to weeks (Fc-fusion typical kinetics)

IgG1-Fc domain confers extended circulation time.

~13 hrSAXENDA (liraglutide) injectio 2014

Duration investigated

12–24 weeks (trial cut short)

—

Standard dose (T2D, Victoza)

—

1.2–1.8 mg / daySAXENDA (liraglutide) injectio 2014

Standard dose (weight, Saxenda)

—

3.0 mg / day (after 5-week titration)SAXENDA (liraglutide) injectio 2014

Frequency

—

Once daily, same time each day

Titration schedule

—

0.6 → 1.2 → 1.8 → 2.4 → 3.0 mg over 5 weeks

Mitigates GI side effects.

Duration

—

Indefinite for chronic indication

Reconstitution

—

Pre-filled commercial pen (no reconstitution)

Timing

—

Any time of day; consistent

04Side Effects & Safety

Parameter

ACE-031

Liraglutide

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 during titration)SAXENDA (liraglutide) injectio 2014

Pancreatitis risk

—

Rare; discontinue if suspected

Thyroid C-cell tumours

—

Boxed warning — contraindicated in MEN2 / MTC historySAXENDA (liraglutide) injectio 2014

Hypoglycemia

—

Low risk as monotherapy; elevated with sulfonylureas / insulin

Heart rate

—

Modest ↑ resting HR (~2-3 bpm)

Cardiovascular benefit

—

↓ MACE in high-risk T2D (LEADER trial)Marso 2016

Pregnancy / OB

—

Contraindicated

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

Liraglutide

·MTC personal or family history; MEN2
·Pregnancy / breastfeeding
·Hypersensitivity to liraglutide

Relative Contraindications

ACE-031

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

Liraglutide

·Severe gastroparesis
·History of pancreatitis
·Severe gastrointestinal disease

05Administration Protocol

Parameter

ACE-031

Liraglutide

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.

Commercial pre-filled pen, no reconstitution required.

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 sites.

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 daily, same time each day. Take with or without food.

4. Clinical trial route

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

Refrigerate 2–8 °C unopened; room temp ≤30 °C up to 30 days after first use.

5. Needle

—

Pen-supplied 32G needle.