Side-by-side · Research reference
MK-677vsSermorelin
Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.
APhase 2Reviewed13/45 cited
BPhase 3Reviewed14/43 cited
MK-677
Oral GHS · Ibutamoren
Oral capsule · 1×/day
Sermorelin
GHRH 1-29 fragment · Short-acting
SQ · Pre-sleep · 1×/day
01Mechanism of Action
Parameter
MK-677
Sermorelin
Pathway
GHS-R1a → Gαq → Ca²⁺ → sustained GH pulses across 24 hrNass 2008
GHRH-R → Gαs → cAMP → PKA → GH vesicle exocytosisWalker 1994
Downstream effect
Sustained GH + IGF-1 elevation; appetite stimulation; lean mass preservationNass 2008
Pulsatile GH release; subsequent IGF-1 elevationMolteno 2013
Feedback intact?
Pulsatile pattern preserved despite long half-lifeMurphy 1998
Yes — short pulse preserves feedback
Origin
Non-peptide spiroindane-piperidine small molecule designed at MerckMurphy 1998
Unmodified active 29-AA fragment of human GHRH (1-44)Walker 1994
Antibody development
—
—
02Dosage Protocols
Parameter
MK-677
Sermorelin
Standard dose
10–25 mg / day oralNass 2008
25 mg used in Nass 2008 elderly trial; 10–15 mg common community dose.
100–500 mcg per injectionMolteno 2013
Frequency
Once daily, oral
Once daily, pre-sleep
Lower / starter dose
5 mg / day
100 mcg per dose
Evidence basis
Phase 2 trials (Nass 2008, Murphy 1998)Nass 2008Murphy 1998
Phase 3 (Geref pediatric); clinical practiceWalker 1994Molteno 2013
Duration
8–16 weeks per cycle (off-cycle to reset receptor sensitivity)
8–12 weeks per cycle
Reconstitution
Oral, no reconstitution
Bacteriostatic water
Timing
Pre-sleep preferred for natural GH pulse alignment
Pre-sleep, fasted preferred
Half-life
~24 hrNass 2008
Once-daily dosing covers 24 hours.
~12 min (plasma)Molteno 2013
Shorter than tesamorelin (~26 min) — simpler GHRH analogue.
04Side Effects & Safety
Parameter
MK-677
Sermorelin
Increased appetite
Strong appetite increase via ghrelin agonism
—
Water retention
Mild edema, paresthesias
—
Cancer risk
Contraindicated in active malignancy (GH/IGF-1 axis)
Contraindicated in active malignancy (GH/IGF-1 axis)
Cardiovascular
No clear adverse signal in trials; congestive heart failure caution
—
Drowsiness
Common, especially during initial weeks
—
Pregnancy / OB
Avoid
Avoid
Injection site reaction
—
Mild erythema, transient pain
Flushing / headache
—
Common transient effect
Glucose handling
—
Generally neutral
Absolute Contraindications
MK-677
- ·Active malignancy
- ·Pregnancy / breastfeeding
- ·Disrupted hypothalamic-pituitary axis
- ·Congestive heart failure (caution)
Sermorelin
- ·Active malignancy
- ·Pregnancy / breastfeeding
- ·Disrupted hypothalamic-pituitary axis
Relative Contraindications
MK-677
- ·Untreated diabetes
- ·Pre-diabetes
- ·Severe insulin resistance
Sermorelin
- ·Untreated diabetes
05Administration Protocol
Parameter
MK-677
Sermorelin
1. Form
Capsule or oral solution. No injection.
Add 2 mL bacteriostatic water to 5 mg vial → 2.5 mg/mL = 250 mcg per 0.1 mL.
2. Site
Oral. Take with or without food.
SQ — abdomen or thigh. Rotate sites.
3. Timing
Pre-sleep preferred — aligns with natural GH pulse.
Pre-sleep, fasted.
4. Storage
Capsule: room temp ≤25 °C, dry place.
Lyophilised: room temp, light-protected. Reconstituted: refrigerate ≤30 days.
5. Caveat
Monitor HbA1c every 8–12 weeks during chronic use.
29–31G, 4–8 mm insulin syringe.
06Stack Synergy
MK-677
— 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