Side-by-side · Research reference

DihexavsTesamorelin

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

AAnimal-StrongHUMAN-REVIEWED7/28 cited

BFDA-ApprovedFlagship27/68 cited

Dihexa

Angiotensin IV Analogue · Pre-Clinical

Pre-clinicalDevelopment stage

Rodent onlyEvidence basisBenoist 2014

HGF/c-MetTarget systemWright 2015

Not established — animal studies only

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

Dihexa

Tesamorelin

Primary target

c-Met receptor (HGF receptor tyrosine kinase)

Hypothalamic GHRH receptorsEGRIFTA® (tesamorelin for inje 2010

Pathway

HGF/c-Met receptor activation → downstream signaling cascade → synaptogenesis and dendritic arborization

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

Downstream effect

Induction of dendritic arborization, synapse formation, neurogenesis, and neuroprotection in rodent models

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

Feedback intact?

—

Yes — physiological pulsatility preserved

Origin

Small-molecule angiotensin IV analogue designed to activate HGF/c-Met systemWright 2015

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

Dihexa

Tesamorelin

Human dosing

Not established — no human trials

—

Animal studies

Mouse/rat models only — dosing not translatable to humans

—

Evidence basis

Pre-clinical / Rodent models

RCT / FDA-approvedFalutz 2007 Falutz 2010

Clinical status

No Phase 1, 2, or 3 trials published

—

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

Half-life

—

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

Modified vs native GHRH (7 min t½).

03Metabolic / Fat Loss Evidence

Parameter

Dihexa

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

Dihexa

Tesamorelin

Human safety data

None available — no human clinical trials

—

Theoretical c-Met risks

c-Met receptor activation has been implicated in tumorigenesis; unknown cancer risk profile

—

Pre-clinical tolerability

Not systematically reported in available studies

—

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

Dihexa

·Not approved for human use — research compound only

Tesamorelin

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

Relative Contraindications

Dihexa

·Theoretical contraindication: active or history of malignancy (c-Met pathway involvement in cancer)

Tesamorelin

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

05Administration Protocol

Parameter

Dihexa

Tesamorelin

1. Human administration

No established protocol. Dihexa has not been tested in human subjects. Animal studies used various routes (typically subcutaneous or intraperitoneal in rodents) not translatable to clinical use.

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

2. Legal status

Pre-clinical research compound. Not approved by FDA or any regulatory authority for human use.

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

3. Timing

—

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

4. Storage

—

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

Dihexa

— 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