Side-by-side · Research reference
ACE-031vsCagrilintide
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-REVIEWED35/64 cited
ACE-031
ActRIIB-Fc Fusion · Phase 2 Halted
SQ · Weekly dosing investigated
01Mechanism of Action
Parameter
ACE-031
Cagrilintide
Primary target
Myostatin, GDF11, activin A — TGF-β superfamily ligands
Amylin receptor (AMYR) and calcitonin receptor (CTR) heterodimeric complexesBailey 2026
Pathway
Soluble decoy receptor binds circulating myostatin/TGF-β ligands → prevents ActRIIB activation → SMAD2/3 pathway inhibition
AMYR/CTR agonism → Central satiety signaling → Reduced food intake, delayed gastric emptying, suppressed glucagonBailey 2026
Downstream effect
Disinhibition of myogenic signaling, increased skeletal muscle mass and strength
Central satiety induction, prandial glucagon suppression, reduced caloric intake, weight loss, improved glycemic controlBailey 2026Yamauchi 2026
Feedback intact?
—
Yes — acts via physiological amylin pathways
Origin
Recombinant fusion protein: human ActRIIB extracellular domain + IgG1-Fc fragmentReichel 2025
Second-generation non-aggregating long-acting amylin analogue designed for once-weekly dosingBailey 2026
Antibody development
—
—
02Dosage Protocols
Parameter
ACE-031
Cagrilintide
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 3 RCT (REDEFINE 5), meta-analysis of 3 RCTs (n=3545)Yamauchi 2026Ahmed 2026
Half-life
Days to weeks (Fc-fusion typical kinetics)
IgG1-Fc domain confers extended circulation time.
—
Duration investigated
12–24 weeks (trial cut short)
—
Standard dose (combination)
—
Cagrilintide 2.4 mg + Semaglutide 2.4 mg (CagriSema)Yamauchi 2026
Phase 3 REDEFINE 5 trial dosing.
Monotherapy dosing
—
Dose-dependent, under investigation
Monotherapy trials reported in meta-analysis.
03Metabolic / Fat Loss Evidence
Parameter
ACE-031
Cagrilintide
Weight loss vs semaglutide
—
7.47% greater percentage weight lossAhmed 2026
CagriSema combination vs semaglutide monotherapy (meta-analysis).
Absolute weight change
—
Significantly greater absolute weight reductionAhmed 2026
Mean difference favoring combination therapy.
Glycemic benefit
—
Reduced fasting glucose and HbA1cAhmed 2026
Synergistic effect with semaglutide in combination.
Body composition
—
Predominant fat loss with weight reduction
Mitochondrial function
—
In vitro effects on skeletal muscle mitochondria under metabolic stress conditionsOld 2026
C2C12 myotube study; clinical relevance under investigation.
Key publications
—
REDEFINE 5 (Yamauchi 2026) · Ahmed meta-analysis 2026 · Bailey review 2026Yamauchi 2026Ahmed 2026Bailey 2026
04Side Effects & Safety
Parameter
ACE-031
Cagrilintide
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)
Local reactions possible with subcutaneous administration
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
—
Gastrointestinal
—
Nausea, diarrhea (common with incretin-based therapies)Pardali 2026
Dietary management and nutritional monitoring recommended.
Safety profile
—
Generally consistent with incretin-based therapies
Phase 3 and meta-analysis safety data.
Tolerability
—
Tolerability considerations similar to GLP-1RAs
Muscle preservation
—
Lean mass considerations during weight loss
In vitro mitochondrial effects observed; clinical impact under investigation.
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
Cagrilintide
- ·Hypersensitivity to cagrilintide or formulation components
Relative Contraindications
ACE-031
- ·Coagulation disorders or anticoagulant use (epistaxis risk)
- ·Hereditary hemorrhagic telangiectasia (HHT) family history
- ·Cardiovascular disease (vascular remodeling effects unknown)
Cagrilintide
- ·Severe gastrointestinal disease
- ·History of pancreatitis (incretin-based therapy consideration)
05Administration Protocol
Parameter
ACE-031
Cagrilintide
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.
Once-weekly subcutaneous injection. Long-acting formulation designed for weekly administration schedule.Bailey 2026
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
Co-formulated with semaglutide as CagriSema for single weekly injection combining amylin and GLP-1 receptor agonism.Yamauchi 2026Bailey 2026
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
Subcutaneous — typically abdomen, thigh, or upper arm. Rotate injection sites weekly to minimize local reactions.
4. Clinical trial route
Phase 2 protocol used subcutaneous injections at weekly or biweekly intervals. Exact dosing protocols remain unpublished.
Refrigerate 2–8°C. Follow product-specific storage instructions for pre-filled pens or vials. Protect from light.
5. Dietary considerations
—
Nutritional monitoring recommended during treatment. Dietary management strategies important for tolerability and outcomes.Pardali 2026
06Stack Synergy
ACE-031
— no documented stacks
Cagrilintide
+ Semaglutide
StrongCagrilintide (amylin receptor agonist) and semaglutide (GLP-1 receptor agonist) act on distinct receptor systems to produce synergistic weight loss through complementary mechanisms — central satiety via amylin pathways plus incretin-mediated glucose control and appetite suppression via GLP-1. Co-formulated as CagriSema, this combination demonstrates 7.5% greater weight loss versus semaglutide monotherapy in Phase 3 trials with additional benefits on glycemic control and lipid parameters.
- CagriSema
- Cagrilintide 2.4 mg + Semaglutide 2.4 mg
- Frequency
- Once weekly subcutaneous
- Duration
- 26–52 weeks (trial data)
- Primary benefit
- Enhanced weight loss, improved glycemic control, multi-pathway metabolic modulation