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MK-677

Also known as Ibutamoren, Ibutamoren mesylate, MK-0677, L-163,191, Nutrobal

Not a peptide but an orally active ghrelin receptor agonist raising GH and IGF-1 around the clock.

early-clinical Growth hormone research chemical

At a glance

Category
Growth hormone
Status
research chemical
Route
oral (tablet or capsule); oral bioavailability above 60 percent
Half-life
approximately 4-6 hours, but with daily dosing the rise in IGF-1 persists for 24 hours
Onset
GH and IGF-1 rise within a few days; change in body composition after 2-6 months
Molecular weight
528.7 g/mol (free base); 624.8 g/mol as the mesylate salt

Not approved as a medicine in the US or the EU. Extensively studied clinically by Merck (among others in elderly patients with hip fracture and in GH deficiency), but development was halted without registration. In the US, ibutamoren mesylate sits in category 2 of the FDA's bulk drug substances policy — substances that may present significant safety risks — under both section 503B (added 29 December 2022) and section 503A (added 29 September 2023). The FDA's stated ground is the potential for congestive heart failure in certain patients, citing a randomised placebo-controlled trial of ibutamoren mesylate in patients recovering from hip fracture that was terminated early because of a potential safety signal of congestive heart failure 3. It is otherwise sold as a 'research chemical' and illegally as a sports supplement.

Doping status: Prohibited at all times (WADA S2, growth hormone secretagogues)

Checked against the WADA 2026 Prohibited List. For a specific product and country, Global DRO is the lookup athletes are expected to use — the List names substances, not brand names.

Mechanism of action

MK-677 is emphatically not a peptide. It is an orally active, non-peptide spiropiperidine molecule that acts as a ghrelin mimetic. It sits in this category because pharmacologically it belongs to the same class as the GHRPs — it activates the same receptor — but it is a small synthetic molecule that survives passage through the gut and can therefore be swallowed, whereas peptides such as ipamorelin and GHRP-2 have to be injected.

MK-677 is an agonist of the growth hormone secretagogue receptor type 1a (GHS-R1a), the ghrelin receptor. It increases GH release by raising the amplitude and number of GH pulses while simultaneously suppressing somatostatin tone. It therefore acts through the same receptor as ipamorelin, hexarelin, GHRP-2 and GHRP-6, and through a different receptor from the GHRH analogues (sermorelin, tesamorelin, CJC-1295, mod GRF 1-29). Here too, combining the two classes is synergistic — although an oral agent with 24-hour coverage is difficult to combine in practice with a pulsatile protocol.

The distinguishing feature of MK-677 relative to the injectable GHRPs is its duration of action. Because of the long half-life and continuous receptor occupancy, GH and IGF-1 remain permanently elevated with daily dosing, rather than rising in discrete pulses. That explains both the robust IGF-1 increase and the greater risk of insulin resistance and fluid retention than with short-acting agents.

Selectivity: in clinical research MK-677 raises cortisol transiently, but the rise is generally mild and short-lived and normalises with continued use. Prolactin rises slightly. The most striking additional effect is the strong increase in appetite, comparable to GHRP-6 and far more pronounced than with ipamorelin. For anyone using the agent to build mass that is a desired effect; for anyone aiming at fat loss it is not. The weight gain seen in studies is moreover to a considerable extent fluid.

Negative feedback via IGF-1 and somatostatin remains intact in principle, but the continuous stimulation makes it less effective at maintaining a normal pulse pattern.

What the research shows

Of all the agents in this category, MK-677 is the most extensively studied clinically, with randomised trials running up to two years. That it durably raises GH and IGF-1 and increases lean mass is well demonstrated. What has not been demonstrated is that this translates into clinically relevant benefit: in the large study in older adults, muscle strength did not increase measurably and a sustained rise in fasting glucose occurred. Merck halted development.

Research in humans

Nass et al. (Ann Intern Med 2008) ran a randomised, double-blind, placebo-controlled study in 65 healthy older adults given 25 mg MK-677 per day for two years 1. IGF-1 rose to the level of young adults and lean mass increased by roughly 1.1 kg, but there was no significant increase in muscle strength or functional capacity, and fasting glucose rose persistently by roughly 0.3 mmol/l 1. Earlier studies examined MK-677 in older adults with hip fracture, in catabolic states and in GH deficiency; in none of those programmes was a primary endpoint met that led to registration. Studies of its use in non-alcoholic fatty liver disease are ongoing.

Animal and lab research

Animal studies confirm the dose-dependent rise in GH and IGF-1, the increase in food intake and the effects on bone density. Given the extent of the human evidence, these data add limited value.

Caveats. The main study included 65 participants, all over 60, and was not designed to detect rare side effects. There is no long-term research in young, healthy adults — precisely the group that uses the agent most. The sustained deterioration in glucose metabolism is a consistent finding, not an isolated incident. That a large manufacturer halted the programme after extensive research is informative in itself. Material sold online falls outside registration control; analyses of commercial 'MK-677' products have shown deviant dosages and contaminants.

What it is used for

  • Increasing one's own GH and IGF-1 release without injections
  • Studied in muscle wasting and catabolic states in older adults, in hip fracture recovery and in growth hormone deficiency
  • Studied in non-alcoholic fatty liver disease
  • Outside research: used for muscle mass, appetite, sleep quality and skin and hair quality — claims that have largely not been confirmed in controlled research

Dosing

Dose
In clinical research 10-25 mg per day; 25 mg per day is the dose from the two-year study in older adults. User protocols mention 10-25 mg per day.
Frequency
Once daily, usually before sleep
Route
oral
Duration
Up to 24 months in research. User protocols mention cycles of 8-16 weeks with a break, partly because of the effects on glucose and fluid retention.
  • There is no approved dose. The 25 mg once daily comes from the two-year randomised trial in 65 healthy adults aged 60-81, which never led to registration 1.
  • The claim that IGF-1 barely rises further above 25 mg per day is not established in any published human dose-ranging study; treat it as unverified. What is established at 25 mg is that GH and IGF-1 rose to the levels of healthy young adults 1.
  • Dosing before sleep aligns with the natural nocturnal GH peak and shifts the drowsiness into the night; some users report disturbed sleep instead.
  • Periodic monitoring of fasting glucose is the most important practical measure with long-term use: in the two-year trial fasting blood glucose rose by 0.3 mmol/l and insulin sensitivity decreased 1.
  • The hunger effect is pronounced, though in the two-year trial the increase in appetite subsided after a few months rather than persisting 1. When the goal is fat loss it still works against it early on.
  • A considerable part of the weight gain in the first weeks is fluid retention, not muscle tissue.

These figures describe what the literature and published protocols report. They are not advice and not a dosing instruction.

Protocols

Two-year trial in healthy older adults, Nass 2008

published trial

Source: Annals of Internal Medicine, 2008

Once daily, orally25 mg
Duration2 years, with the primary endpoints assessed at 1 year

65 healthy adults aged 60 to 81. Fat-free mass rose by about 1.1 kg against a 0.5 kg fall on placebo, and GH and IGF-1 were restored to young-adult levels - but the added fat-free mass produced no change in strength or function, fasting glucose rose by about 0.3 mmol/l and insulin sensitivity fell. This is the longest human exposure on record and it is where the 25 mg figure comes from.

MK-677, common user schedule

user protocol — not validated

Source: Pattern reported on forums and by vendors

This is not a validated schedule. It is a pattern that circulates among users and sellers, reproduced because it is what people actually follow — not because it has been tested. No trial established these doses, this interval or this duration, and nobody is checking what is in the vial. Treat every number below as an assertion, not a finding.

Once daily, usually before bed12.5-25 mg orally
Common starting point10-12.5 mg per day, raised to 25 mg if tolerated
Run length8-16 weeks, then a break - usually justified by the effects on glucose and fluid retention

MK-677 is swallowed and is not a peptide, so nothing here involves a vial, reconstitution or a syringe. Above 25 mg per day IGF-1 barely rises further while fluid retention, daytime drowsiness and worsening glucose tolerance do. Much of the weight gained in the first weeks is water rather than tissue, and the appetite increase runs all day rather than briefly, which is the opposite of what a fat-loss goal needs.

Schedules are reproduced as their source states them. Units, IU and milligrams explains why the figures are not interchangeable between products.

Reconstitution

Storage
Store dry, cool and dark. Liquid formulations have a limited shelf life once opened; capsules are more stable.

Not applicable: MK-677 is an orally active non-peptide and does not need to be reconstituted. It is sold as a capsule, tablet or as a solution in a solvent (often polyethylene glycol or an alcohol base). With liquid products the actual concentration is often unreliable.

Safety

Side effects

  • Reduced insulin sensitivity and raised fasting glucose — fasting blood glucose rose by 0.3 mmol/l and insulin sensitivity decreased over the two-year trial. This is the best substantiated side effect 1.
  • Increase in appetite — the most frequent side effect in the two-year trial, where it subsided after a few months 1
  • Transient, mild lower-extremity oedema — also among the most frequent side effects in the two-year trial 1
  • Muscle pain — likewise among the most frequent side effects reported 1
  • Tingling and numbness in the hands; carpal tunnel syndrome is a plausible risk with continuous GH elevation, though it was not among the reported effects in the two-year trial
  • Fatigue and excessive daytime drowsiness
  • Disturbed sleep or vivid dreams in some users
  • A significant rise in cortisol was measured in the two-year trial 1
  • Congestive heart failure — a randomised placebo-controlled trial of ibutamoren mesylate in patients recovering from hip fracture was terminated early because of a potential safety signal of congestive heart failure, and this is the FDA's stated ground for placing the substance in category 2 3
  • Raised blood pressure in a proportion of users
  • Slight rises in liver enzymes have been reported
  • A reduction in LDL cholesterol was seen in research, but this is not a demonstrated clinical benefit

Do not use if

  • Active or previously treated malignancy — GH and IGF-1 are growth factors and the concern that they may stimulate existing malignant cells is theoretical but has not been refuted. With MK-677 this concern weighs more heavily than with short-acting agents, because the IGF-1 elevation is continuous and prolonged.
  • Diabetes mellitus type 1 or type 2, prediabetes and impaired glucose tolerance — given the demonstrated fall in insulin sensitivity and rise in fasting glucose 1
  • Congestive heart failure, or risk factors for it — the hip fracture recovery trial was stopped early over a potential congestive heart failure signal, and this is the FDA's stated significant safety risk for the substance 3
  • Active diabetic retinopathy
  • Pregnancy and breastfeeding
  • Children and adolescents with open growth plates, outside medical supervision
  • Severe acute illness, after open heart surgery or in acute respiratory failure
  • Eating disorders or situations in which an uncontrolled increase in appetite is harmful
  • Untreated hypertension

Interactions

Raised GH and IGF-1 reduce insulin sensitivity; in people using insulin or oral antidiabetics the requirement for these may increase. Growth hormone accelerates the conversion of cortisol to cortisone via 11-beta-HSD-1, which can increase hydrocortisone requirements in adrenal insufficiency, and it can affect the conversion of T4 to T3 — thyroid values may shift as a result. Somatostatin analogues block GH release. MK-677 is metabolised via CYP3A4, so strong CYP3A4 inhibitors (ketoconazole, ritonavir, clarithromycin) can increase exposure and strong inducers (rifampicin, St John's wort, carbamazepine) can reduce it. Concurrent use with other agents that cause fluid retention increases the risk of oedema.

Common questions

What is MK-677 (ibutamoren)?
An orally active ghrelin-receptor agonist — a tablet, not a peptide — that raises growth hormone and IGF-1 and keeps them elevated around the clock.
What are the side effects of MK-677?
The steady rise in IGF-1 is commonly linked to water retention, increased appetite and lethargy, and at higher exposure to reduced insulin sensitivity. It is an unapproved research chemical — see the safety section above.
Is MK-677 a SARM or a steroid?
Neither. It is a growth-hormone secretagogue that works through the ghrelin receptor. It is often sold alongside SARMs but is a different class.
Is MK-677 banned in sport?
Yes — growth-hormone secretagogues are on the WADA Prohibited List (S2) and banned at all times. Compare it with the injectable option at MK-677 vs ipamorelin.

Sources