Side-by-side · Research reference

HexarelinvsRetatrutide

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

APhase 1Reviewed19/45 cited

BPhase 2Reviewed10/41 cited

Hexarelin

Hexapeptide GHRP · Cardio-tropic

100–200 mcgPer doseSmith 1996

Phase 1Evidence levelGhigo 1997

~70 minHalf-lifeSemenistaya 2010

SQ · Multiple sites · 1–3×/day

Retatrutide

Triple-receptor agonist · Phase 3

1–12 mgWeekly doseJastreboff 2023

24.2%Body-weight ↓Jastreboff 2023

~6 daysHalf-life (est)

SQ · Abdomen · Once weekly

01Mechanism of Action

Parameter

Hexarelin

Retatrutide

Primary target

Ghrelin receptor (GHS-R1a) + cardiac CD36Smith 1996 Ghigo 1997

GLP-1R + GIPR + Glucagon receptor (triple agonism)Jastreboff 2023

Pathway

GHS-R1a → Gαq → Ca²⁺ → GH release. CD36 engagement → direct cardio-tropic actionGhigo 1997

Triple-receptor activation → ↑insulin (GLP-1+GIP), ↓gastric emptying, ↑lipid handling, ↑energy expenditure (glucagon component)Jastreboff 2023

Downstream effect

Strong GH pulse + IGF-1 elevation; cardio-protective effects in animal MI modelsGhigo 1997

Maximal weight loss across class. Glucagon component drives lipolysis and energy expenditure beyond GLP-1+GIP aloneJastreboff 2023

Feedback intact?

Yes initially; tachyphylaxis with chronic useGhigo 1997

—

Origin

Synthetic hexapeptide His-D-2-Methyl-Trp-Ala-Trp-D-Phe-Lys-NH₂Smith 1996

Synthetic peptide engineered for balanced affinity at three incretin / glucagon receptorsJastreboff 2023

Antibody development

—

02Dosage Protocols

Parameter

Hexarelin

Retatrutide

Standard dose

100–200 mcg per injectionSmith 1996

12 mg / week (max efficacy)Jastreboff 2023

Phase 2 trial dose. Phase 3 dosing TBD.

Frequency

1–2× per day max (tachyphylaxis with chronic 3× daily)

Once weekly

Lower / starter dose

50 mcg per dose

—

Evidence basis

Phase 1 / Phase 2 trialsSmith 1996 Ghigo 1997

Phase 2 trial; Phase 3 ongoingJastreboff 2023

Duration

4–8 weeks on / 4–8 weeks off (tachyphylaxis mitigation)

Indefinite for chronic indication (presumed)

Reconstitution

Bacteriostatic water

Investigational; not commercially available

Timing

Pre-sleep + fasted preferred

Any time of day

Half-life

~70 minSemenistaya 2010

~6 days (estimated from class)

Titration schedule

—

2 mg → 4 mg → 8 mg → 12 mg over 16 weeks

04Side Effects & Safety

Parameter

Hexarelin

Retatrutide

Cortisol elevation

Modest at high dosesGhigo 1997

—

Prolactin elevation

Modest at high dosesGhigo 1997

—

Hunger

Strong appetite increase via ghrelin agonism

—

Tachyphylaxis

Receptor desensitisation with chronic dosingGhigo 1997

—

Cardiac effects

Direct cardio-tropic; potential benefit in MI but unstudied in humansGhigo 1997

—

IGF-1 elevation

Strong; monitor with chronic high-dose use

—

Cancer risk

Contraindicated in active malignancy (GH/IGF-1 axis)

—

Pregnancy / OB

Avoid

Avoid (insufficient data)

GI symptoms

—

Nausea, vomiting, diarrhea (very common, dose-dependent)Jastreboff 2023

Heart rate

—

↑ resting HR (3–7 bpm at 12 mg)Jastreboff 2023

Glucose handling

—

Glycemic improvement; rare hyperglycemia from glucagon component

Pancreatitis risk

—

Class warning

Thyroid C-cell tumours

—

Class warning (presumed)

Absolute Contraindications

Hexarelin

·Active malignancy
·Pregnancy / breastfeeding
·Disrupted hypothalamic-pituitary axis

Retatrutide

·MTC personal or family history (presumed class effect)
·Pregnancy / breastfeeding

Relative Contraindications

Hexarelin

·Untreated diabetes
·Severe hyperprolactinemia

Retatrutide

·Severe gastroparesis
·History of pancreatitis
·Severe cardiovascular disease (HR signal)

05Administration Protocol

Parameter

Hexarelin

Retatrutide

1. Reconstitution

Add 2 mL bacteriostatic water to 5 mg vial → 2.5 mg/mL = 250 mcg per 0.1 mL.

Investigational peptide. Research vials reconstituted with bacteriostatic water per label.

2. Injection site

SQ — abdomen or thigh. Rotate sites.

SQ — abdomen, thigh, or upper arm. Rotate weekly.

3. Timing

Pre-sleep + fasted preferred. Cycle on/off to avoid tachyphylaxis.

Once weekly, same day.

4. Storage

Lyophilised: room temp, light-protected. Reconstituted: refrigerate ≤30 days.

Refrigerate 2–8 °C. Light-protected.

5. Needle

29–31G, 4–8 mm insulin syringe.

27–31G, 4–8 mm insulin syringe.

06Stack Synergy

Hexarelin

+ CJC-1295 (no DAC)

Strong

View CJC-1295 (no DAC) →

Hexarelin (GHRP) + CJC-1295-no-DAC (GHRH analogue) is the higher-amplitude variant of the standard GHRH+GHRP stack. Hexarelin produces a stronger pulse than ipamorelin but with cortisol + prolactin signal — choose this stack for maximum GH amplitude when side-effect tolerance is acceptable. Cycle aggressively.

Hexarelin: 100 mcg SQ · pre-sleep
CJC-1295 (no DAC): 100 mcg SQ · same injection
Primary benefit: Maximum GH pulse amplitude (with side-effect signal)

Smith 1996 Teichman 2006

Retatrutide

— no documented stacks