Side-by-side · Research reference
RetatrutidevsSermorelin
Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.
APhase 2Reviewed10/41 cited
BPhase 3Reviewed14/43 cited
Retatrutide
Triple-receptor agonist · Phase 3
SQ · Abdomen · Once weekly
Sermorelin
GHRH 1-29 fragment · Short-acting
SQ · Pre-sleep · 1×/day
01Mechanism of Action
Parameter
Retatrutide
Sermorelin
Primary target
GLP-1R + GIPR + Glucagon receptor (triple agonism)Jastreboff 2023
Pituitary GHRH receptorWalker 1994
Pathway
Triple-receptor activation → ↑insulin (GLP-1+GIP), ↓gastric emptying, ↑lipid handling, ↑energy expenditure (glucagon component)Jastreboff 2023
GHRH-R → Gαs → cAMP → PKA → GH vesicle exocytosisWalker 1994
Downstream effect
Maximal weight loss across class. Glucagon component drives lipolysis and energy expenditure beyond GLP-1+GIP aloneJastreboff 2023
Pulsatile GH release; subsequent IGF-1 elevationMolteno 2013
Feedback intact?
—
Yes — short pulse preserves feedback
Origin
Synthetic peptide engineered for balanced affinity at three incretin / glucagon receptorsJastreboff 2023
Unmodified active 29-AA fragment of human GHRH (1-44)Walker 1994
Antibody development
—
—
02Dosage Protocols
Parameter
Retatrutide
Sermorelin
Standard dose
12 mg / week (max efficacy)Jastreboff 2023
Phase 2 trial dose. Phase 3 dosing TBD.
100–500 mcg per injectionMolteno 2013
Frequency
Once weekly
Once daily, pre-sleep
Titration schedule
2 mg → 4 mg → 8 mg → 12 mg over 16 weeks
—
Evidence basis
Phase 2 trial; Phase 3 ongoingJastreboff 2023
Phase 3 (Geref pediatric); clinical practiceWalker 1994Molteno 2013
Duration
Indefinite for chronic indication (presumed)
8–12 weeks per cycle
Reconstitution
Investigational; not commercially available
Bacteriostatic water
Timing
Any time of day
Pre-sleep, fasted preferred
Half-life
~6 days (estimated from class)
~12 min (plasma)Molteno 2013
Shorter than tesamorelin (~26 min) — simpler GHRH analogue.
Lower / starter dose
—
100 mcg per dose
04Side Effects & Safety
Parameter
Retatrutide
Sermorelin
Glucose handling
Glycemic improvement; rare hyperglycemia from glucagon component
Generally neutral
Pancreatitis risk
Class warning
—
Thyroid C-cell tumours
Class warning (presumed)
—
Pregnancy / OB
Avoid (insufficient data)
Avoid
Injection site reaction
—
Mild erythema, transient pain
Flushing / headache
—
Common transient effect
IGF-1 elevation
—
Modest at standard doses
Cancer risk
—
Contraindicated in active malignancy (GH/IGF-1 axis)
Absolute Contraindications
Retatrutide
- ·MTC personal or family history (presumed class effect)
- ·Pregnancy / breastfeeding
Sermorelin
- ·Active malignancy
- ·Pregnancy / breastfeeding
- ·Disrupted hypothalamic-pituitary axis
Relative Contraindications
Retatrutide
- ·Severe gastroparesis
- ·History of pancreatitis
- ·Severe cardiovascular disease (HR signal)
Sermorelin
- ·Untreated diabetes
05Administration Protocol
Parameter
Retatrutide
Sermorelin
1. Reconstitution
Investigational peptide. Research vials reconstituted with bacteriostatic water per label.
Add 2 mL bacteriostatic water to 5 mg vial → 2.5 mg/mL = 250 mcg per 0.1 mL.
2. Injection site
SQ — abdomen, thigh, or upper arm. Rotate weekly.
SQ — abdomen or thigh. Rotate sites.
3. Timing
Once weekly, same day.
Pre-sleep, fasted.
4. Storage
Refrigerate 2–8 °C. Light-protected.
Lyophilised: room temp, light-protected. Reconstituted: refrigerate ≤30 days.
5. Needle
27–31G, 4–8 mm insulin syringe.
29–31G, 4–8 mm insulin syringe.
06Stack Synergy
Retatrutide
— no documented stacks
Sermorelin
+ Ipamorelin
StrongSermorelin (GHRH analogue) and ipamorelin (selective GHRP) form the prototypical GHRH+GHRP dual-axis stack at the lowest cost. Both peak within 30 min and produce a sharp physiological GH pulse without cortisol/prolactin elevation.
- Sermorelin
- 200–300 mcg SQ · pre-sleep
- Ipamorelin
- 200–300 mcg SQ · same injection
- Primary benefit
- Pulsatile GH stimulation, recovery, body composition