Side-by-side · Research reference

PE 22-28vsTesamorelin

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

AAnimal-StrongHUMAN-REVIEWED16/47 cited

BFDA-ApprovedFlagship27/68 cited

PE 22-28

TREK-1 Antagonist · Pre-Clinical

0.12 nMTREK-1 IC50Djillani 2017

7 AAPeptide lengthDjillani 2017

AnimalEvidence stage

IP · SQ · Once Daily (animal models)Djillani 2017 Pietri 2019

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

PE 22-28

Tesamorelin

Primary target

TREK-1 two-pore-domain potassium channelDjillani 2017 Ma 2020

Hypothalamic GHRH receptorsEGRIFTA® (tesamorelin for inje 2010

Pathway

TREK-1 channel blockade → Neuronal membrane depolarisation → Enhanced hippocampal excitability → Increased neuroplasticity

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

Downstream effect

Antidepressant-like activity in forced swim test and tail suspension test; reduced A1-like reactive astrocyte activation; neuroprotection via NF-κB pathway modulationDjillani 2017 Cong 2023 Wu 2021

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

Feedback intact?

N/A — direct ion channel blockade; not receptor-mediated endocrine axis

Yes — physiological pulsatility preserved

Origin

Synthetic truncation of spadin (PE 12-28), itself derived from the sortilin propeptide C-terminus. Residues 22-28: Val-Val-Arg-Gly-Trp-Leu-Arg.Djillani 2017 Mazella 2018

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

Antibody development

Not reported in animal studies

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

02Dosage Protocols

Parameter

PE 22-28

Tesamorelin

Animal dose (antidepressant)

0.3–3 µg/kg IP

Effective in forced swim test, tail suspension test, CUMS models.

—

Animal dose (neuroprotection)

0.03 µg/kg IPPietri 2019

Low-dose TREK-1 activation post-stroke for 7 days, then high-dose blockade.

—

Frequency

Once daily

Sustained antidepressant effect over 7+ days.

Once daily (morning or pre-sleep)

Aligns with natural GH pulse.

Onset (animal)

Within hours (acute); full effect 4–7 days

—

Duration (animal)

7–28 days testedQi 2018 Pietri 2019

—

Comparison to fluoxetine

PE 22-28 outperforms fluoxetine in CUMS-sensitive rats by day 7

Chronic administration shows superior long-term efficacy.

—

Human equivalent (extrapolated)

Not established — no clinical trials

Allometric scaling from rodent data unavailable.

—

Evidence basis

Multiple rodent RCTs; behavioral + electrophysiology endpointsDjillani 2017 Qi 2018 Wu 2021

RCT / FDA-approvedFalutz 2007 Falutz 2010

Standard dose

—

2 mg / dayEGRIFTA® (tesamorelin for inje 2010

FDA-approved protocol.

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

PE 22-28

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

PE 22-28

Tesamorelin

Toxicity (animal)

No adverse effects reported at therapeutic doses

—

Cardiovascular (theoretical)

TREK-1 expressed in cardiac tissue; arrhythmia risk unclear

—

Weight change

Not reported in animal studies

—

Neurological

No seizures or behavioral abnormalities noted

—

Long-term safety

Unknown — longest animal study 28 days

—

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

PE 22-28

·Human use — no clinical safety data available

Tesamorelin

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

Relative Contraindications

PE 22-28

·Cardiac arrhythmia or channelopathy (theoretical TREK-1 cardiac role)

Tesamorelin

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

05Administration Protocol

Parameter

PE 22-28

Tesamorelin

1. Animal protocol (IP)

Dissolved in sterile saline or vehicle. Intraperitoneal injection, 0.3–3 µg/kg body weight. Once daily administration in rodent behavioral studies.

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

2. Stability

Shorter peptide length (7 AA) confers improved plasma stability vs 17-AA spadin. Exact storage conditions not detailed in published protocols.Djillani 2017

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

3. BBB penetration

Enhanced CNS bioavailability vs full spadin, likely due to smaller size. Mechanism (passive diffusion vs active transport) not fully characterized.

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

4. Human formulation

Not established — peptide synthesis methods for research use only. No pharmaceutical-grade formulation available.

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

PE 22-28

— 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