On this page
What it is
A non-peptide, orally bioavailable growth-hormone secretagogue with a long half-life, developed through a full clinical programme that did not lead to approval.
How it is proposed to work
Ghrelin receptor agonism producing sustained rather than pulsatile elevation of growth hormone and IGF-1. The sustained profile is the key pharmacological difference from injectable secretagogues, and is likely relevant to its metabolic effects.
Approved medical uses
None. MK-677 has no approved human medical indication in the jurisdictions we track. Any use is outside an approved label.
Human research
Each entry states what the study found and, separately, what it cannot show.
- Randomised controlled trial2008n = 65
Two-year randomised trial of oral MK-677 in healthy older adults
Finding. One primary endpoint was met and the other was not. Over 12 months, once-daily oral MK-677 raised growth hormone and IGF-1 to the levels of healthy young adults, and mean fat-free mass rose by 1.1 kg against a fall of 0.5 kg on placebo (P < 0.001). There was no significant difference in abdominal visceral fat — the second primary endpoint — or in total fat mass, while limb fat rose more on MK-677 than on placebo (1.1 kg vs 0.24 kg, P = 0.001) and body weight rose 2.7 kg against 0.8 kg (P = 0.003). Fasting blood glucose rose and insulin sensitivity decreased. The authors state plainly that the increased fat-free mass did not result in changes in strength or function.
Limitation. Sixty-five adults aged 60 to 81 at a single university centre. The authors' own stated limitation is that study power, in both duration and participant number, was insufficient to evaluate functional endpoints — so the absence of a strength or function benefit here is a failure to detect one, not a demonstration that none exists. Fat-free mass is a body-composition measure, not a clinical outcome. The metabolic direction was unfavourable: fasting glucose rose, insulin sensitivity fell, and cortisol rose. Reported side effects were an increase in appetite that subsided within months, and transient mild lower-limb oedema and muscle pain.
- Randomised controlled trial2008n = 563
Trial in Alzheimer's disease
Finding. No benefit on cognitive or functional endpoints.
Limitation. A well-powered negative trial. Relevant because it demonstrates the compound was seriously tested and did not deliver.
Preclinical research
Animal and laboratory work. Useful for generating hypotheses; it cannot establish that something works in people.
No preclinical studies catalogued.
Potential safety concerns
- CautionEstablished
Increased fasting glucose and reduced insulin sensitivity are consistently reported. This is the best-documented adverse effect and it follows directly from the mechanism.
- CautionEstablished
Fluid retention and oedema are common, particularly early. Some of the 'lean mass' gain on a scale is water.
- WatchEstablished
Marked appetite increase. Useful in a wasting context; counterproductive if the goal is fat loss.
- CautionEstablished
Sold widely as a supplement, which it is not. It is an unapproved drug, and it is prohibited in sport.
Known interactions and contraindication considerations
- Effects on glucose handling matter for anyone with diabetes, prediabetes or on glucose-lowering therapy.
- Fluid retention is relevant in heart failure or uncontrolled hypertension.
This list is not exhaustive and is not a substitute for a clinician reviewing your full medication history.
Regulatory status
Status is shown per jurisdiction and is accurate only as of the date stated. Where a compound is approved, the approval is bound to a specific formulation, manufacturer and indication — shown in the detail column.
| Jurisdiction | Standing | Detail |
|---|---|---|
United States FDA | Not approved as of 1 Jun 2026 | Development did not result in approval. Widely sold as a 'research chemical' or mislabelled as a supplement, which it is not. |
European Union EMA | Unapproved / investigational as of 1 Jun 2026 | No marketing authorisation. |
India CDSCO | Unapproved / investigational as of 1 Jun 2026 | Not approved for human use. |
How it is being used
What the grey community actually runs, the reasoning they give, and our read on whether it follows from known biology. This is observation, not evidence, and not a recommendation.
Oral growth-hormone elevation, appetite and sleep
What is run
Taken orally once daily, commonly at night, in blocks of several weeks to months. Widely reported for appetite and sleep as much as for body composition.
Their mechanistic reasoning
That oral dosing and a long half-life give sustained IGF-1 elevation without injections, and that the appetite increase is useful in a surplus.
Reported in the community’s own terms. Not our position.
Stacked with
- Injectable secretagogues—Layered for a pulse on top of sustained elevation, though the two profiles are pharmacologically at odds.
- A caloric surplus—The appetite effect is used deliberately here.
Regimen shape
- Dose
- figure withheld
- Scale
- Milligram-scale
- Route
- Oral
- Frequency
- Once daily
- Timing
- Commonly at night, partly for the sleep effect
- Duration
- Blocks of weeks to months
Our read
The pharmacology is accurate — it does exactly what is claimed to IGF-1, and conveniently. The problem is that this is the one compound in the class where the outcome question was actually answered. Trials in older adults showed lean mass rising without corresponding gains in strength or function, and an Alzheimer's trial was negative. Meanwhile the metabolic cost is consistent and documented. Buying mass without function, at the price of insulin sensitivity, is a worse trade than the community treats it as.
What the community reports
The comparison is between how sure the community is and how much is actually known — evidence strength, not direction. A compound can have solid research that came out negative.
Genuinely contested, and the split is informative. Enthusiasts cite sleep and appetite; critics cite glucose and water retention. Both camps are describing real, documented effects — they simply weigh them differently.
Commonly reported as helping
- Markedly deeper sleep, the most consistent report
- Strong appetite increase, useful in a surplus
- Rapid weight gain in the first weeks
- Improved skin and nail quality
Also reported, when it goes wrong
- Water retention and puffiness, very widely reported
- Rising fasting glucose in people who measure it
- Lethargy and daytime grogginess
- Numbness and tingling in the hands
- Increased hunger reported as unmanageable by some
Why these reports can mislead
Early weight gain is substantially water, and it is frequently reported as muscle. This is the clearest case in the library of a real effect being misattributed — and the trials answered it directly: lean mass rose without a matching gain in strength or function.
Direct quotations are not published here yet. We will only carry verbatim reports once they are sourced, dated and checked — an unattributed quote is a testimonial, and testimonials are exactly what this section exists to replace.
Watch for, in this use specifically
- Fasting glucose and insulin sensitivity worsen consistently. Measure them, and stop if they move badly.
- Early weight gain is substantially water. It is not lean mass, whatever the scale says.
- Prohibited in sport, and sold as a supplement despite being an unapproved drug.
Active clinical trials
No registered trials currently tracked for MK-677.
What remains unknown
The questions that would change our assessment if they were answered.
- Is there any population in which the lean-mass gain produces functional benefit?
- Are the insulin-sensitivity effects fully reversible on stopping?
- Does the sustained-elevation profile carry different long-term risk from pulsatile secretagogues?
References
- 1.Nass R, Pezzoli SS, Oliveri MC, et al. Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial. Ann Intern Med. 2008.PMID 18981485doi
- 2.Sevigny JJ, Ryan JM, van Dyck CH, Peng Y, Lines CR, Nessly ML. Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trial. Neurology. 2008.PMID 19015485doi
Editorial change history
When we change a grade or a regulatory note, we log it here rather than editing quietly.
Regraded from Preliminary to Tested, no benefit. The earlier grade implied an evidence gap; the trials were in fact adequately powered and answered the question negatively. This compound is why the grade was added.
Dossier created. Graded Preliminary rather than Promising: the human trials are good quality and largely negative on function.
Spotted something wrong? Tell us — we publish corrections.