Side-by-side · Research reference

ACE-031vsTesamorelin

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-ApprovedFlagship27/68 cited

ACE-031

ActRIIB-Fc Fusion · Phase 2 Halted

Phase 2Highest trial stage

2011Development halted

~58.4 kDaMolecular weightReichel 2025

SQ · Weekly dosing investigated

Tesamorelin

GHRH Analogue · FDA-Approved

2 mgDaily doseEGRIFTA® (tesamorelin for inje 2010

15–20%VAT reductionFalutz 2010

~26 minHalf-lifeEGRIFTA® (tesamorelin for inje 2010

SQ · Abdomen · Once Daily

01Mechanism of Action

Parameter

ACE-031

Tesamorelin

Primary target

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

Hypothalamic GHRH receptorsEGRIFTA® (tesamorelin for inje 2010

Pathway

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

GHRH → Pituitary GH release → Liver IGF-1 synthesisFalutz 2007

Downstream effect

Disinhibition of myogenic signaling, increased skeletal muscle mass and strength

Increased GH pulsatility, elevated IGF-1, lipolysis of visceral adipose tissueFalutz 2010

Feedback intact?

—

Yes — physiological pulsatility preserved

Origin

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

Synthetic 44-AA GHRH analogue with trans-3-hexenoic-acid modification for stabilityEGRIFTA® (tesamorelin for inje 2010

Antibody development

—

~50% after 26 wks (non-neutralising in most)Sévigny 2018

02Dosage Protocols

Parameter

ACE-031

Tesamorelin

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

RCT / FDA-approvedFalutz 2007 Falutz 2010

Half-life

Days to weeks (Fc-fusion typical kinetics)

IgG1-Fc domain confers extended circulation time.

~26 min (plasma)EGRIFTA® (tesamorelin for inje 2010

Modified vs native GHRH (7 min t½).

Duration investigated

12–24 weeks (trial cut short)

—

Standard dose

—

2 mg / dayEGRIFTA® (tesamorelin for inje 2010

FDA-approved protocol.

Frequency

—

Once daily (morning or pre-sleep)

Aligns with natural GH pulse.

Lower / starter dose

—

1 mg / dayFalutz 2010

1 mg still produces significant IGF-1 elevation.

Duration

—

12–52 weeks

VAT returns within months of stopping.

Reconstitution

—

Sterile water per labeling

Preserved at 2–8 °C after reconstitution.

Timing

—

Empty stomach, pre-sleep preferred

03Metabolic / Fat Loss Evidence

Parameter

ACE-031

Tesamorelin

Primary fat target

—

Visceral adipose tissue (VAT) — abdominal

Quantified reduction

—

15–20% VAT ↓Falutz 2010

By CT at 26 weeks (Falutz et al., NEJM).

IGF-1 impact

—

+66 ng/mL (2 mg dose) · +81% mean elevationFalutz 2007

Effect on lean mass

—

Modest lean mass preservation / slight increase

Insulin sensitivity

—

Neutral to slight impairment (monitor HbA1c)Clarke 2018

Triglycerides

—

Significant TG reduction noted in Phase 3Falutz 2010

Glucose metabolism

—

Generally neutral; 4.5% HbA1c elevation riskClarke 2018

Effect reversibility

—

VAT returns within months of stopping

Key publication

—

Falutz et al. NEJM 2007 · Falutz JCEM 2010 · FDA approval 2010Falutz 2007 Falutz 2010 EGRIFTA® (tesamorelin for inje 2010

04Side Effects & Safety

Parameter

ACE-031

Tesamorelin

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

—

Injection site reaction

—

Erythema, pruritus, redness (common)

Fluid retention / Edema

—

Peripheral edema, arthralgia, carpal tunnel (GH-axis effect)

Glucose intolerance

—

HbA1c ↑ in 4.5% vs 1.3% placebo; HbA1c ≥6.5% hazard OR 3.3Clarke 2018

IGF-1 elevation

—

Dose-dependent; supraphysiological levels = discontinue

Cancer risk

—

Contraindicated in active malignancy (GH/IGF-1 axis); theoretical tumour growth riskEGRIFTA® (tesamorelin for inje 2010

Antibody formation

—

~50% at 26 weeks; non-neutralising in most; rare hypersensitivity (<1%)Sévigny 2018

GI symptoms

—

Nausea, diarrhea (mild, transient)

Pregnancy / OB

—

ContraindicatedEGRIFTA® (tesamorelin for inje 2010

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

Tesamorelin

·Active malignancy or history of treated cancer
·Pregnancy
·Hypersensitivity to tesamorelin or mannitol
·Disruption of hypothalamic-pituitary axis (trauma, tumour, radiation)

Relative Contraindications

ACE-031

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

Tesamorelin

·Untreated diabetes (monitor HbA1c)
·Severe carpal tunnel syndrome
·Acute critical illness

05Administration Protocol

Parameter

ACE-031

Tesamorelin

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.

Add 2.1 mL sterile water to 2 mg lyophilised vial. Roll gently — do not shake. Solution should be clear.

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 preferred. Rotate sites (avoid same spot within 2 cm). Avoid navel and waistband area.

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. Preferred: evening, 2–3 hrs post-meal, before sleep — aligns with natural GH secretion pulse.

4. Clinical trial route

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

Lyophilised: room temp, light-protected. Reconstituted: refrigerate 2–8 °C, use within 21 days.

5. Needle

—

27–31G, 4–8 mm insulin syringe. Pinch skin, 45° angle for lean individuals.

06Stack Synergy

ACE-031

— no documented stacks

Tesamorelin

+ Ipamorelin

Strong

View Ipamorelin →

Tesamorelin (GHRH analogue) and ipamorelin (GHRP / ghrelin mimetic) act on two distinct receptor systems to amplify GH release synergistically — GHRH receptor + ghrelin receptor. This dual-axis stimulation produces a more robust, sustained GH pulse than either alone while maintaining physiological pulsatility. Ipamorelin is highly selective with minimal cortisol or prolactin elevation, making it the preferred GHRP pairing.

Tesamorelin: 2 mg SQ · evening
Ipamorelin: 200–300 mcg SQ · same injection
Frequency: Once daily, pre-sleep
Primary benefit: Maximal GH pulsatility, fat loss, recovery, sleep quality

Raun 1998