Side-by-side · Research reference
ACE-031vsSurvodutide
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 3HUMAN-REVIEWED25/54 cited
ACE-031
ActRIIB-Fc Fusion · Phase 2 Halted
SQ · Weekly dosing investigated
Survodutide
GLP-1/Glucagon Dual Agonist · Phase 3
SQ · Once Weekly
01Mechanism of Action
Parameter
ACE-031
Survodutide
Primary target
Myostatin, GDF11, activin A — TGF-β superfamily ligands
GLP-1 receptor and glucagon receptor (GCGR)Yathindra 2026Zimmermann 2026
Pathway
Soluble decoy receptor binds circulating myostatin/TGF-β ligands → prevents ActRIIB activation → SMAD2/3 pathway inhibition
Central: CVOs → hypothalamic appetite regulation. Peripheral: GLP-1R → incretin effect; GCGR → hepatic lipid metabolism, energy expenditureZimmermann 2026Long 2026
Downstream effect
Disinhibition of myogenic signaling, increased skeletal muscle mass and strength
Decreased energy intake, increased energy expenditure, improved glucose homeostasis, hepatic fat reductionZimmermann 2026Yathindra 2026
Feedback intact?
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Origin
Recombinant fusion protein: human ActRIIB extracellular domain + IgG1-Fc fragmentReichel 2025
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Antibody development
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02Dosage Protocols
Parameter
ACE-031
Survodutide
Clinical dosing
Weekly or biweekly SQ injections (exact doses undisclosed pre-halt)
Phase 2 DMD trial protocol not fully published.
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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
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Evidence basis
Phase 2 trial discontinued — incomplete dataset
Phase 2 RCT (obesity) · Phase 3 ongoing
Half-life
Days to weeks (Fc-fusion typical kinetics)
IgG1-Fc domain confers extended circulation time.
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Duration investigated
12–24 weeks (trial cut short)
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Frequency
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Once weekly
03Metabolic / Fat Loss Evidence
Parameter
ACE-031
Survodutide
Primary fat target
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Total body weight, visceral adipose tissue
Weight loss mechanism
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Dual action: decreased energy intake + increased energy expenditureZimmermann 2026
Phase 2 efficacy
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Significant weight loss demonstrated
Specific percentage not disclosed in abstracts.
Metabolic markers
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Improvements in ALT, AST, LDL levels; significant ALT reduction (MD -22.10 vs placebo)Yathindra 2026Abulehia 2026Andonie 2026
Network meta-analysis
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Favorable efficacy profile vs other glucagon receptor agonists
Comparative efficacy
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Network meta-analysis shows competitive efficacy in GRA class
04Side Effects & Safety
Parameter
ACE-031
Survodutide
Epistaxis (nosebleeds)
Significant incidence in Phase 2 DMD trial — primary safety signal
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Telangiectasia
Dilated capillaries / spider veins observed
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Vascular abnormalities
Mechanism: ActRIIB/ALK1 pathway disruption affects vascular homeostasis
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Injection site reactions
Local erythema, induration (biologics class effect)
Expected with subcutaneous administration
Antibody development
Potential for anti-drug antibodies (Fc-fusion proteins); incidence not reported
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Black market contaminants
12/14 tested products contained multiple unidentified proteins alongside ACE-031Reichel 2025
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GI symptoms
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Diarrhea, nausea, fatigue — class effect of GLP-1 agonists
Safety profile
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Network meta-analysis: comparable safety to other GRAs
Serious adverse events
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Monitored in Phase 2/3; no unique safety signals reported
Detailed SAE data pending Phase 3 completion.
Glucagon-related effects
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Potential for tachycardia, increased blood pressure — theoretical glucagon effect
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
Survodutide
- ·Personal or family history of medullary thyroid carcinoma (class effect)
- ·Multiple endocrine neoplasia syndrome type 2
Relative Contraindications
ACE-031
- ·Coagulation disorders or anticoagulant use (epistaxis risk)
- ·Hereditary hemorrhagic telangiectasia (HHT) family history
- ·Cardiovascular disease (vascular remodeling effects unknown)
Survodutide
- ·Severe GI disease (inflammatory bowel disease, gastroparesis)
- ·History of pancreatitis
- ·Cardiovascular disease (monitor closely for glucagon effects)
05Administration Protocol
Parameter
ACE-031
Survodutide
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.
Specific reconstitution protocol not yet publicly disclosed. Follow manufacturer instructions upon approval.
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
Subcutaneous — abdomen, thigh, or upper arm. Rotate sites weekly to minimize injection site reactions.
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 each week. Can be administered at any time of day, with or without meals.
4. Clinical trial route
Phase 2 protocol used subcutaneous injections at weekly or biweekly intervals. Exact dosing protocols remain unpublished.
Store refrigerated (2–8 °C) until use. Do not freeze. Protect from light. Specific reconstituted storage duration pending labeling.
5. Needle
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Subcutaneous injection with appropriate gauge needle (typically 27–31G). Use sterile technique.