Compound Physician required WADA prohibited

MK-677 (Ibutamoren)

Oral GH secretagogue — reliably raises GH/IGF-1, but also reliably raises insulin resistance.

The story

MK-677 began as a medicinal-chemistry problem rather than a biological discovery, and the drug arrived before its target was understood. In 1993 a Merck group reported L-692,429, a non-peptidyl benzolactam that released growth hormone through the same alternative pathway as the growth hormone-releasing hexapeptide GHRP-6 rather than through growth hormone-releasing hormone (Science 1993, DOI 10.1126/science.8503009). Two years later the same program described a far more potent successor: L-163,191, subsequently MK-0677 and then ibutamoren. It released GH from cultured rat pituitary cells with an EC50 of 1.3 nM and elevated GH in dogs after oral doses as low as 0.125 mg/kg — a canine dose. It is not a human dose, and it is not convertible into one: do not scale it by bodyweight or by any allometric factor. No human quantity is derivable from it, and none is derived anywhere in this file. The same paper reported no meaningful effect on aldosterone, luteinizing hormone, thyroxine or prolactin (PNAS 1995, DOI 10.1073/pnas.92.15.7001). Oral activity was the entire design objective, and it was achieved by abandoning the peptide backbone altogether — the reason MK-677 sits so oddly alongside the injectable peptides it is marketed with.

The order of events is worth stating plainly, because it inverts the usual one. The synthetic agonist came first. The receptor it acted on, GHS-R1a, was cloned in 1996 using these compounds as the probe (Science 1996, DOI 10.1126/science.273.5277.974), and the receptor's endogenous ligand, ghrelin, was not identified until 1999 (Nature 1999, DOI 10.1038/45230). MK-677 is therefore a ghrelin mimetic that predates the discovery of ghrelin by four years.

Merck's clinical program was serious, sustained and unusually well designed for a compound that now circulates as a research chemical. Between 1996 and 2008, randomized double-blind placebo-controlled trials tested MK-677 in healthy elderly adults, in GH-deficient adults and children, in obese men, in postmenopausal osteoporosis, in diet-induced catabolism, in hip-fracture recovery, and in Alzheimer's disease. The biochemical result was consistent across every one of them: IGF-1 rose, often dramatically, and pulsatile GH secretion was amplified rather than replaced. The clinical result was consistent too, and it was negative. A 161-patient international hip-fracture trial raised IGF-1 by 84% and produced no statistically significant improvement in functional performance (JAGS 2004, DOI 10.1111/j.1532-5415.2004.52156.x). A 563-patient, 12-month Phase 3 in mild-to-moderate Alzheimer's disease raised IGF-1 by 72.9% and did not slow disease progression on any of four endpoints (Neurology 2008, DOI 10.1212/01.wnl.0000335163.88054.e7). A two-year trial in healthy older adults added 1.1 kg of fat-free mass and produced no change in strength or function (Ann Intern Med 2008, DOI 10.7326/0003-4819-149-9-200811040-00003). A later 123-patient Phase 2b in hip-fracture recovery was terminated early for a congestive heart failure safety signal (Arch Gerontol Geriatr 2011, DOI 10.1016/j.archger.2010.10.004). FDA's own review records the compound's development as discontinued, with "insufficient data to establish effectiveness of ibutamoren mesylate for use in treating GHD" (FDA PCAC briefing document, 2024). The molecule did not fail because it was under-studied. It failed because it was studied and did not work at the endpoints its sponsors chose.

The rights did not die with the program. Ibutamoren was later taken up as LUM-201 by a company registered under the name Lumos Pharma, and a Phase 3 trial in pediatric growth hormone deficiency stands registered and listed as recruiting (NCT06948214 — T2 — registry record, self-asserted, unverified; status re-verified against the registry API on 2026-08-29). "Lumos Pharma" is the name on the registry record and on that company's own pipeline page, and nothing else corroborates it — under R-A that is a registration existing under a given name, not evidence that the named entity ran a trial. The same company separately states the molecule has been "studied in more than 1300 patients (more than 150 children)" (Lumos Pharma pipeline page — T3 — per sponsor announcement; a T3 source may never carry a safety or efficacy figure, and this patient count is carried only as an attributed sponsor claim). Those are two statements by one entity and count as one source, not two. What the pair establishes is that a registration exists and what its sponsor says about it — not that the programme is well conducted, not that the patient count is right, and not that it will read out.

The route into fitness culture ran through the online research-chemical market rather than through clinics. Because MK-677 is an orally active small molecule with a simple published synthesis and a large public efficacy literature, it became, in the words of an equine doping-control paper, "one of the most prevalent performance-enhancing compounds currently available online" (Drug Test Anal 2023, DOI 10.1002/dta.3406). It is sold predominantly by vendors who also sell selective androgen receptor modulators, under the trade-ish names Nutrobal and Oratrope, labelled "for research use only" — a framing FDA has repeatedly rejected in warning letters, finding that website marketing claims established the products were "intended to be drugs for human use" and therefore unapproved new drugs (FDA warning letter, 2025-12-12). The consequences show up in the case literature: a published account of a recreational user co-administering LGD-4033 and MK-677 with adverse changes in bone, lipids, liver enzymes and testosterone (Exp Physiol 2022, DOI 10.1113/EP090741), a 2025 report of MK-677-associated hepatotoxicity (BMJ Case Rep, DOI 10.1136/bcr-2025-265728), and a 2026 report of spontaneous splenic rupture in a man using MK-677 with RAD-140 (Cureus 2026, DOI 10.7759/cureus.106106). It has also reached athletes who never sought it: two of the four verified US anti-doping sanctions naming ibutamoren arose from contaminated over-the-counter supplements.

  1. 1993 Merck reports L-692,429, the first non-peptidyl GH secretagogue, acting through the GHRP pathway rather than GHRH
  2. 1995 L-163,191 (MK-0677) described — orally active, EC50 1.3 nM at rat pituitary cells, GH release in dogs at 0.125 mg/kg orally (a canine dose — not a human dose and not convertible to one)
  3. 1996 GHS-R cloned in pituitary and hypothalamus using these secretagogues as probes
  4. 1996 First human dose-ranging trial in 32 healthy adults aged 64–81; IGF-1 restored to young-adult range at the highest dose tested, fasting glucose rose
  5. 1998 MK-677 shown to reverse diet-induced negative nitrogen balance in a crossover trial in 8 healthy volunteers
  6. 1999 Ghrelin identified as the endogenous ligand of the receptor MK-677 had been designed against four years earlier
  7. 2001 18-month, 292-woman osteoporosis trial with alendronate reports MK-677's effects on bone turnover and BMD
  8. 2004 161-patient international hip-fracture trial: IGF-1 +84%, no significant functional benefit
  9. 2008 2-year RCT in 65 healthy older adults published in Annals of Internal Medicine: fat-free mass up, fasting glucose up, insulin sensitivity down, no change in strength or function
  10. 2008 Phase 3 in 563 Alzheimer's patients fails on all efficacy endpoints despite 72.9% IGF-1 increase
  11. 2011 123-patient Phase 2b in hip fracture terminated early for a congestive heart failure safety signal; authors conclude "MK-0677 has an unfavorable safety profile in this patient population"
  12. 2019, 2021 Two US athletes sanctioned for ibutamoren, both traced to contaminated over-the-counter supplements
  13. 2024-10-29 FDA Pharmacy Compounding Advisory Committee votes 1–13 against placing ibutamoren mesylate on the 503A bulk drug substances list
  14. 2025–2026 Case reports of MK-677-associated hepatotoxicity and of splenic rupture during MK-677 + SARM use enter the literature
  15. 2026 A Phase 3 trial of ibutamoren as LUM-201 in pediatric growth hormone deficiency is registered under the name Lumos Pharma and listed as recruiting — a registration, not a result

What it does

An oral GH secretagogue that reliably raises GH and IGF-1 — and just as reliably raises insulin resistance. The metabolic trade-off is the single most consistent finding in its human trial record, not a footnote.

An orally active ghrelin-receptor agonist. Unlike the injectable secretagogues it needs no injection, but it produces a more sustained, less pulsatile GH/IGF-1 elevation — the likely driver of its metabolic side effect.

  • growth hormone
  • IGF-1
  • lean mass

What the evidence shows

Merck ran real randomized, double-blind, placebo-controlled trials on this molecule, at scale and for long durations: a two-year RCT in 65 healthy older adults, an 18-month osteoporosis trial in 292 women, and a 12-month phase 3 in 563 patients with Alzheimer's disease that failed on all four efficacy endpoints and is the single most informative long-term safety dataset the compound has. Those trials establish with unusual confidence that MK-677 raises GH and IGF-1 and adds fat-free mass — and, in the same participants over the same months, that it reliably increases appetite, causes lower-extremity edema, raises fasting glucose and reduces insulin sensitivity, and that the added lean tissue never converted into strength, physical function, cognition, quality of life or fracture recovery at any endpoint any sponsor chose to measure. The problem with the evidence on MK-677 is not that it is absent; it is that it shows the things the marketing omits. The limitation that matters is population and supervision: no randomized trial has ever enrolled a healthy young adult training for body composition, which is essentially the entire current user base, and there is no lawful US channel through which anyone could take it under the monitoring that produced these findings in the first place.

Overall evidence strength: Moderate certainty

  • Nass R, Pezzoli SS, Oliveri MC, et al. (2008) — two-year RCT in healthy older adults (2008) Randomized controlled trial

    Over a year, MK-677 restored GH and IGF-1 to young-adult levels and added about 1.1 kg of fat-free mass while placebo lost 0.5 kg — and that extra lean tissue produced no measurable improvement in strength, physical function, or quality of life, while fasting glucose rose, insulin sensitivity fell, body weight rose 2.7 kg, and limb fat increased more than in the placebo group. It is the cleanest demonstration in the literature that the biomarker moves and the person does not.

    Source PMID 18981485

  • Sevigny JJ, Ryan JM, van Dyck CH, et al. (2008) — Phase 3 in Alzheimer's disease (2008) Randomized controlled trial

    In the largest and longest MK-677 trial ever run, serum IGF-1 rose 60.1% at six weeks and 72.9% at twelve months — proof the drug was doing exactly what it was supposed to do — and patients did no better than placebo on any measure of cognition, daily function or global impression. This is the single most informative long-duration human dataset on the compound, and it is informative mostly about safety and about the gap between a biomarker and a benefit.

    Source PMID 19015485

  • Adunsky A, Chandler J, Heyden N, et al. (2011) — Phase 2b in hip-fracture recovery, terminated early (2011) Randomized controlled trial

    IGF-1 rose by 51.4 ng/mL against placebo and gait speed improved slightly, but most functional measures did not move, and the trial was stopped early because more patients on MK-677 developed congestive heart failure — four (6.5%) versus one (1.7%) on placebo. The authors' conclusion is unusually blunt: "MK-0677 has an unfavorable safety profile in this patient population."

    Source PMID 21067829

  • Chapman IM, Bach MA, Van Cauter E, et al. (1996) — first human dose-ranging trial (1996) Randomized controlled trial

    MK-677 amplified the body's own GH pulses rather than replacing them — pulse height and trough concentrations rose, the number of pulses did not — and at the highest dose tested it brought IGF-1 from 141 to 265 µg/L over four weeks. In the same four weeks fasting glucose rose from 5.4 to 6.8 mmol/L (P < 0.01), which is the metabolic cost, measured in the very first human study. Cortisol did not change; prolactin rose 23% but stayed within the normal range.

    Source PMID 8954023

  • Murphy MG, Plunkett LM, Gertz BJ, et al. (1998) — reversal of diet-induced catabolism (1998) Randomized controlled trial

    In healthy people deliberately underfed, MK-677 flipped nitrogen balance from negative to slightly positive (+0.31 vs −1.48 g/day, P < 0.01) — the clearest evidence that it spares protein during caloric restriction, in eight people over seven days, which is a mechanism demonstration rather than a clinical result. Peak GH after a single dose was 55.9 µg/L, falling to 22.6 µg/L after a week of dosing.

    Source PMID 9467534

  • Murphy MG, Weiss S, McClung M, et al. (2001) — 18-month osteoporosis trial (2001) Randomized controlled trial

    Adding a GH secretagogue to a bisphosphonate did not deliver the extra bone density the hypothesis predicted; MK-677 raised markers of bone turnover — both formation and resorption — which is not the same as building bone. This is the largest and longest look at MK-677's skeletal effects and it is the reason "increases bone density" is a weaker claim than it sounds.

    Source PMID 11238495

  • Supporting human trials worth knowing about

    - Hip fracture, 161 patients, 6 months' treatment + 6 months' follow-up, 13 centres across seven countries. IGF-1 +84% (95% CI 63–107) versus +17% on placebo; no significant difference in functional performance or overall Sickness Impact Profile. Diabetic patients and patients with congestive heart failure were excluded at entry. DOI 10.1111/j.1532-5415.2004.52156.x

    Source

  • What the reviews say

    A 2018 review of GH secretagogue safety and efficacy concludes the class is generally well tolerated "with some concern for increases in blood glucose because of decreases in insulin sensitivity," and that "few long-term, rigorously controlled studies have examined the efficacy and safety of GHSs" (DOI 10.1016/j.sxmr.2017.02.004). A 2020 review of GHS in hypogonadal men found "a paucity of data examining the clinical effects of these compounds currently limits our understanding" (DOI 10.21037/tau.2019.11.30).

    Source

Common misconceptions

“MK-677 gives you the benefits of growth hormone without the downsides.”

The premise is half right, and the half that is wrong is the half the marketing omits. MK-677 does raise GH and IGF-1 physiologically — it amplifies the body's own pulses rather than flooding the system with exogenous hormone (DOI 10.1210/jcem.81.12.8954023) — and it does add fat-free mass (DOI 10.7326/0003-4819-149-9-200811040-00003). But the same randomized trials that documented those effects also documented the metabolic and fluid costs, in the same participants, at the same doses. In the two-year Annals of Internal Medicine trial, fasting glucose rose, insulin sensitivity fell, body weight rose 2.7 kg, limb fat rose more than in placebo, cortisol rose by 47 nmol/L, and the most frequent side effects were "an increase in appetite that subsided in a few months and transient, mild lower-extremity edema and muscle pain." In the first human dose-ranging study, four weeks at the highest dose tested moved mean fasting glucose from 5.4 to 6.8 mmol/L (P < 0.01) (DOI 10.1210/jcem.81.12.8954023). A 2018 review of the class concludes GH secretagogues are "well tolerated, with some concern for increases in blood glucose because of decreases in insulin sensitivity" (DOI 10.1016/j.sxmr.2017.02.004). Members of FDA's Pharmacy Compounding Advisory Committee, voting 1–13 against compounding eligibility, cited "adverse effects reported including fluid retention, congestive heart failure, and hyperglycemia" (PCAC minutes, 2024-10-29). Honest answer: MK-677's effects and its side effects are not separable — they are the same pharmacology. Appetite increase is ghrelin-receptor agonism working as designed. Fluid retention is a known GH effect. Reduced insulin sensitivity is the metabolic signature of sustained GH elevation. Anyone describing MK-677 as "GH without the side effects" is describing a compound that has not been tested, because the compound that was tested produced those effects in trial after trial. ⚠️ Unresolved: how big is the glucose effect? Chapman et al. 1996 report mean fasting glucose rising from 5.4 to 6.8 mmol/L over four weeks at the highest dose tested in 32 adults aged 64–81 — roughly 25 mg/dL. Nass et al. 2008 report an average rise of only 0.3 mmol/L (5 mg/dL) over a year at the same dose in 65 adults aged 60–81. Same dose, similar populations, a fivefold difference in effect size. Both are peer-reviewed; neither explains the other. We report both and do not resolve it. The direction is consistent across the literature; the magnitude is not.

“MK-677 is a SARM.”

It is not, and the confusion is a marketing artifact rather than a scientific one. Selective androgen receptor modulators act on the androgen receptor; MK-677 is a spiroindoline sulfonamide agonist at the ghrelin receptor (GHS-R1a) with no androgen-receptor activity (DOI 10.1073/pnas.92.15.7001). Anti-doping classification makes the distinction explicit: SARMs sit in S1.2, Other Anabolic Agents, alongside andarine, ostarine, LGD-4033 and RAD140, while ibutamoren sits in S2.2.4, growth hormone secretagogues, under Peptide Hormones, Growth Factors, Related Substances and Mimetics (2026 Prohibited List — T1 — regulator document; text verified against JADCO's hosted copy of that same WADA document, which is a hosted copy of WADA's own document, not an independent source — one document, two URLs, and the second confirms transcription accuracy only). The confusion has a concrete source: MK-677 is sold predominantly by vendors whose catalogues are otherwise SARMs, and FDA warning letters to those vendors list it among their unapproved drug products (FDA, 2025-12-12). It is also frequently co-administered with SARMs — both published case reports involving MK-677 in recreational users describe concurrent LGD-4033 or RAD-140 use (DOI 10.1113/EP090741; DOI 10.7759/cureus.106106). Neither being sold alongside something nor being taken alongside it makes it that thing. Why it matters practically: the two classes have different biomarker signatures and different monitoring implications. In the published LGD-4033 + MK-677 case report, the changes to serum lipids, liver enzymes and testosterone are attributable to a SARM, not to a GH secretagogue — but a user who believes MK-677 "is a SARM" will misattribute in both directions.

“It shuts down your natural GH production, so you have to cycle it.”

No trial has documented suppression of endogenous GH secretion by MK-677, and the mechanism argues against it. MK-677 works by amplifying pre-existing pulsatile GH release — pulse height and interpulse trough concentrations rise while the number of pulses does not change (DOI 10.1210/jcem.81.12.8954023) — and GH release remains subject to IGF-1 negative feedback, which is the pharmacological argument for secretagogues over exogenous GH in the first place (DOI 10.1016/j.sxmr.2017.02.004). What is documented is attenuation of the acute GH spike with continued dosing: peak GH was 55.9 µg/L after a single dose and 22.6 µg/L after a week of daily dosing in the same subjects (DOI 10.1210/jcem.83.2.4551). That is feedback restraining an amplified signal, not a shut-down somatotroph — and IGF-1 stayed elevated for a full two years of continuous dosing in the Annals trial with no loss of effect (DOI 10.7326/0003-4819-149-9-200811040-00003). The honest limit: no trial has measured GH or IGF-1 after stopping MK-677. "What happens when you stop" is genuinely undocumented, so the cycling argument is neither supported nor refuted by evidence — it is simply unstudied.

“The lean mass gain is muscle.”

Some of it is water, and none of it has been shown to be usable. The two-year trial measured fat-free mass by DXA and body cell mass by intracellular water; fat-free mass rose 1.1 kg and intracellular water rose 0.8 kg, meaning much of the compartment that DXA calls "lean" was fluid. In the same participants, "increased fat-free mass did not result in changes in strength or function," and total body weight rose 2.7 kg while limb fat rose significantly more than placebo (DOI 10.7326/0003-4819-149-9-200811040-00003). The hip-fracture trials tested the same proposition directly in people who needed the function, and neither found a significant functional benefit (DOI 10.1111/j.1532-5415.2004.52156.x; DOI 10.1016/j.archger.2010.10.004). Note also what is genuinely supported: in eight calorically restricted volunteers, MK-677 flipped nitrogen balance from negative to positive over seven days (DOI 10.1210/jcem.83.2.4551). Protein-sparing during a deficit is the best-supported anabolic claim MK-677 has, and it rests on eight people for one week.

“It builds bone density.”

It increases bone turnover, which is not the same claim. Across three trials in 187 elderly adults, MK-677 raised both bone formation markers (osteocalcin, bone-specific alkaline phosphatase) and the resorption marker urinary N-telopeptide (DOI 10.1359/jbmr.1999.14.7.1182); the same bidirectional pattern appeared in obese young men (DOI 10.1359/jbmr.1998.13.7.1158). The hypothesis that pairing MK-677 with a resorption inhibitor would capture the formation side and produce superior BMD was tested properly — 292 women, 18 months, randomized, placebo-controlled — and the Annals trial separately recorded only "changes in bone mineral density consistent with increased bone remodeling" (DOI 10.1210/jcem.86.3.7294; DOI 10.7326/0003-4819-149-9-200811040-00003). A compound that accelerates both sides of remodeling is not straightforwardly a bone-building drug.

“Merck dropped it for business reasons, not because it failed.”

Merck ran the trials and the trials read out negative on their prespecified endpoints. The Alzheimer's Phase 3 (n=563) missed on all four measures despite a 72.9% IGF-1 increase (DOI 10.1212/01.wnl.0000335163.88054.e7). Both hip-fracture trials missed on function, and the second was stopped early for congestive heart failure (DOI 10.1111/j.1532-5415.2004.52156.x; DOI 10.1016/j.archger.2010.10.004). FDA's review concluded there is "insufficient data to establish effectiveness of ibutamoren mesylate for use in treating GHD" and that the criteria "weigh against placing ibutamoren mesylate on the list of bulk drug substances that can be used to compound drug products" (FDA briefing document). Ibutamoren also did not vanish: a Phase 3 trial of the same molecule, as LUM-201, is registered under the name Lumos Pharma and listed as recruiting in pediatric GH deficiency (NCT06948214 — T2 — registry record, self-asserted, unverified; existence and status only; the registration and the Lumos pipeline page are two statements by one entity and count as one source, and nothing outside those two corroborates the sponsor's identity or the programme). That a current registration exists is difficult to reconcile with a suppression narrative — though a registration is a record, not a result, and it says nothing about whether the programme will succeed. ⚠️ Unresolved date. FDA's briefing document states development "was discontinued in 1999," but Merck Sharp & Dohme is the sponsor of MK-677 trials that started in 2003 (NCT00074529) and 2005 (NCT00128115) — named as such in the peer-reviewed reports of both, not only in the registry fields. Either the 1999 date refers to a specific indication programme or the summary is imprecise. Unresolved; carried forward. ---

Who it's for, who should skip

Experimental, physician-supervised only. Status is gray_zone — never FDA-approved, cannot lawfully be sold as a supplement, WADA-prohibited. It reliably raises insulin resistance, a real consideration for anyone with metabolic risk. Not for anyone with active or recent cancer, or who is pregnant.

Skip it if

  • active or recent cancer — GH-axis stimulation can accelerate tumor growth. hard block
  • pregnancy — Contraindicated in pregnancy. hard block

Running it

No dosing protocol is published for this compound — there is no lawful supervised channel for the use this guide covers. What follows is monitoring, expectations, and safety framing only.

Form
oral

What to expect

  • Acute (hours, first dose) — Peak GH of ~55.9 µg/L after a single oral dose in healthy young volunteers, against ~9 µg/L on placebo (Confidence: Trial-documented (DOI 10.1210/jcem.83.2.4551))
  • Days 1–7 — Acute GH peak attenuates with repeat dosing (55.9 → 22.6 µg/L by day 7) while the effect on nitrogen balance is already measurable; sleep-architecture changes recorded within 7 days in a 14-person crossover (Confidence: Trial-documented, small n (DOI 10.1210/jcem.83.2.4551; DOI 10.1159/000127249))
  • Weeks 2–6 — IGF-1 up substantially and measurably — +52% in GH-deficient adults after 4 days; +60.1% at 6 weeks in the Alzheimer's trial; bone turnover markers up within 2 weeks. Appetite increase reported as the most frequent early effect (Confidence: Trial-documented (DOI 10.1210/jcem.82.10.4297; DOI 10.1212/01.wnl.0000335163.88054.e7; DOI 10.1359/jbmr.1999.14.7.1182))
  • Weeks 4–8 — Fasting glucose rise measurable by 4 weeks. Free T3 rise and peak TSH rise detectable by 8 weeks in obese men; leptin rise present at 2 weeks and gone by 8 (Confidence: Trial-documented (DOI 10.1210/jcem.81.12.8954023; DOI 10.1046/j.1365-2265.1999.00667.x))
  • Months 3–12 — Fat-free mass gain of ~1.1 kg versus a 0.5 kg loss on placebo; total weight +2.7 kg; limb fat +1.1 kg; IGF-1 sustained at +72.9% at 12 months. No change in isokinetic strength, physical function, or quality of life at any point (Confidence: Trial-documented (DOI 10.7326/0003-4819-149-9-200811040-00003; DOI 10.1212/01.wnl.0000335163.88054.e7))
  • Plateau — Appetite increase is described as subsiding "in a few months"; edema and muscle pain as "transient." IGF-1 elevation did not attenuate — two-year exploratory analyses confirmed the one-year results (Confidence: Trial-documented (DOI 10.7326/0003-4819-149-9-200811040-00003))
  • Post-cessation — Not studied. No trial measured GH, IGF-1, body composition or glucose after stopping. The 2004 hip-fracture trial followed patients for 6 months after treatment ended but reported function, not hormone or metabolic recovery (Confidence: No data (DOI 10.1111/j.1532-5415.2004.52156.x))
  • Long-term (>2 years) — No data in any population. The longest randomized exposure on record is 2 years in 65 healthy older adults; the largest is 12 months in 563 Alzheimer's patients (Confidence: No data)
  • Long-term in healthy young adults — No data at any duration. No randomized trial has enrolled this population (Confidence: No data)

Response signs

Likely working

  • Marked increase in appetite, often within days — Trial-documented — the most frequently reported effect in a 2-year RCT, and the direct pharmacological consequence of ghrelin-receptor agonism · DOI 10.7326/0003-4819-149-9-200811040-00003 Trial-documented
  • Deeper, less fragmented sleep; more slow-wave sleep — Trial-documented but small — polysomnography in 8 young and 6 older adults over 7–14 days · DOI 10.1159/000127249 Trial-documented
  • Weight gain on the scale over weeks to months — Trial-documented — +2.7 kg at 12 months, of which fat-free mass, intracellular water and limb fat all contributed · DOI 10.7326/0003-4819-149-9-200811040-00003 Trial-documented
  • Preserved lean tissue while eating at a deficit — Trial-documented but very small — n=8, 7 days, healthy young volunteers under supervised caloric restriction · DOI 10.1210/jcem.83.2.4551 Trial-documented
  • Feeling stronger / better performance in training — Anecdotal, low confidence — the dominant claim in circulation. Randomized trials measuring isokinetic strength and physical function found no change · DOI 10.7326/0003-4819-149-9-200811040-00003 Anecdotal
  • Faster injury or tendon recovery — Anecdotal, low confidence — a 2026 scoping review of peptides in sports medicine found human clinical studies for this class "limited to a handful of investigations, most lacking robust controls" · DOI 10.1177/03635465261464420 Anecdotal

Adverse — seek review

  • Swelling of the ankles, feet or lower legs; rings or shoes becoming tight — Trial-documented — lower-extremity edema was among the most frequent adverse effects; fluid retention was cited by FDA advisory committee members · DOI 10.7326/0003-4819-149-9-200811040-00003; PCAC minutes Trial-documented
  • Breathlessness on exertion or lying flat, rapid weight gain over days, new orthopnea — Trial-documented safety signal — congestive heart failure occurred in 6.5% on drug vs 1.7% on placebo in frail elderly hip-fracture patients and terminated that trial. Not evaluated in healthy adults, which is a reason for caution, not reassurance · DOI 10.1016/j.archger.2010.10.004; FDA briefing document Trial-documented
  • Increased thirst, increased urination, or a rising fasting glucose reading — Trial-documented — fasting glucose rose and insulin sensitivity fell in randomized trials; note that people with diabetes were excluded from the trials, so the effect in that group is unmeasured · DOI 10.7326/0003-4819-149-9-200811040-00003; DOI 10.1111/j.1532-5415.2004.52156.x Trial-documented
  • Persistent right-upper-quadrant discomfort, jaundice, dark urine, or unexplained fatigue — Case report, single patient — transaminitis after two months' use in an otherwise healthy man, resolving on cessation. Weak evidence of causation; sufficient reason to check · DOI 10.1136/bcr-2025-265728
  • Severe acute abdominal pain, especially left upper quadrant — Case report, single patient, confounded — spontaneous splenic rupture in a 54-year-old man using MK-677 with RAD-140. Presented by the authors as a possible contributing risk factor, not an established cause · DOI 10.7759/cureus.106106
  • Numbness, tingling, carpal-tunnel-type symptoms, or new joint pain — Trial-documented for muscle and joint pain; the numbness/tingling pattern is listed among reported effects by DoD's supplement-safety programme rather than in a trial report · DOI 10.7326/0003-4819-149-9-200811040-00003; OPSS Trial-documented

Common / neutral

  • Appetite increase easing after a few months while other effects persist — Trial-documented — described in the 2-year RCT as subsiding "in a few months" · DOI 10.7326/0003-4819-149-9-200811040-00003 Trial-documented
  • The acute "GH pulse" sensation fading after the first week — Trial-documented at the hormone level — peak GH fell from 55.9 to 22.6 µg/L between day 1 and day 7 of dosing. This is feedback, not tolerance to the IGF-1 effect, which persisted for two years · DOI 10.1210/jcem.83.2.4551; DOI 10.7326/0003-4819-149-9-200811040-00003 Trial-documented
  • Nausea, diarrhea, transient lethargy — Listed by DoD's supplement-safety programme; not prominent in the randomized trial reports · OPSS
  • Scale weight rising faster than visible muscle — Trial-documented — fat-free mass, intracellular water and limb fat all rose; visceral fat and total fat mass did not fall · DOI 10.7326/0003-4819-149-9-200811040-00003 Trial-documented

Getting it right

  • Monitoring: This compound has a real biomarker map, which changes what monitoring means. Unlike most of this batch, MK-677 has markers that reliably move in both directions. Monitoring here is not a formality — it is the only way to see the trade-off that the randomized trials documented. mitigate side effect
  • Monitoring: Glucose and insulin sensitivity are the defining watch items. Fasting glucose rose and insulin sensitivity fell in randomized trials at the dose that circulates (DOI 10.7326/0003-4819-149-9-200811040-00003), and a 2018 class review names this as the principal safety concern for GH secretagogues (DOI 10.1016/j.sxmr.2017.02.004). Note that people with diabetes were excluded from the major trials, so the trial literature says nothing about them. mitigate side effect
  • Monitoring: Fluid status is the second. Edema was among the most frequent trial-reported effects, and the severe form of it — congestive heart failure — terminated a trial (DOI 10.1016/j.archger.2010.10.004). mitigate side effect
  • Monitoring: A pre-exposure baseline is what makes any of this interpretable. Trials measured glucose, insulin sensitivity, lipids, cortisol, bone markers, thyroid indices and body composition before and then on a schedule. A single measurement taken after months of use cannot distinguish a drug effect from a starting point. mitigate side effect
  • Monitoring: IGF-1 confirms exposure, not benefit. It rises reliably and by a large margin; it did so in the Alzheimer's trial where nothing else improved, and in both hip-fracture trials where function did not improve. Treat a high IGF-1 as evidence the compound is in the system, not as evidence it is helping. mitigate side effect
  • Monitoring: HbA1c and any long-term glycemic endpoint are unmeasured in the entire literature. That is a gap in the evidence, not a reassurance. mitigate side effect
  • General safety: Product identity is a live risk even though the molecule is well characterized. Two of the four verified US anti-doping sanctions naming ibutamoren arose from over-the-counter supplements the athletes did not know contained it — which establishes that MK-677 has been present, undeclared, in products sold as ordinary supplements. FDA warning letters document the same substance being sold under "research use only" labelling with human-use marketing claims (FDA). mitigate side effect
  • General safety: The congestive heart failure signal deserves to be understood precisely rather than dismissed or exaggerated. It was observed in frail, post-operative, elderly hip-fracture patients — a population selected for fluid-handling vulnerability — and the earlier trial in a similar population had excluded people with heart failure at entry (DOI 10.1111/j.1532-5415.2004.52156.x). It has never been evaluated in healthy adults. It is neither established as a general risk nor excluded as one. mitigate side effect
  • General safety: Combination use is where the documented harms in recreational users appear. Both published case reports involve co-administration with a SARM, and DoD warns specifically about this combination (OPSS; DOI 10.1113/EP090741; DOI 10.7759/cureus.106106). Adverse events in a multi-compound regimen cannot be attributed to any one component. mitigate side effect
  • General safety: Athletes and service members face strict liability. MK-677 is prohibited at all times in sport and is on the DoD prohibited dietary supplement ingredients list; contamination is not a defence that avoids a sanction, only one that may reduce it. mitigate side effect
  • The physician conversation: What specifically is the goal — appetite, sleep, lean mass, recovery, "anti-ageing"? Each has a different evidence base, and only appetite and IGF-1 are strongly documented. mitigate side effect
  • The physician conversation: What is the fasting glucose, and has insulin sensitivity ever been assessed? (— this is the trade-off the trials measured.) mitigate side effect
  • The physician conversation: Is there any personal or family history of diabetes, insulin resistance, heart failure, or fluid-retention problems? (People with diabetes and with heart failure were excluded from the trials that generated the reassuring numbers.) mitigate side effect
  • The physician conversation: What else is being taken, particularly anything from a SARM vendor? (Both published case reports of harm involve co-administration.) mitigate side effect
  • The physician conversation: What would count as it working, measured how, and by when — and what happens at that date if the answer is no? (Note that the trials that measured strength and function found no change.) mitigate side effect
  • The physician conversation: Is there any competitive sport, collegiate, or military testing obligation? (. Two of the documented sanctions came from contaminated supplements, not intentional use.) mitigate side effect
  • The physician conversation: Has liver function been checked, and would it be checked again? (, case-level evidence only, but cheap to look at.) mitigate side effect

Measuring it

Retest IGF-1 — Baseline, then on a clinician-set schedule — no guideline sets an IGF-1 interval for this agent, and the rhGH cadence is not borrowed. Include glucose and HbA1c: MK-677 raises insulin resistance..

  • IGF-1 baseline
  • IGF-1 on cycle
  • Fasting glucose baseline
  • Fasting glucose on cycle
  • HbA1c baseline
  • HbA1c quarterly

How biomarkers respond

  • Fasting glucose May deteriorate · 4 weeks to 12 months — Up — +0.3 mmol/L (5 mg/dL) over 12 months (P = 0.015) in one RCT; 5.4 → 6.8 mmol/L over 4 weeks (P < 0.01) in another — Trial-documented, direction replicated, magnitude disputed (see ⚠️ below) (DOI 10.7326/0003-4819-149-9-200811040-00003; DOI 10.1210/jcem.81.12.8954023) Trial-documented
  • Cortisol May deteriorate · 4 weeks – 12 months — Conflicting — up 47 nmol/L (95% CI 28–71; P = 0.020) in the 2-year RCT; no change in the 1996 dose-ranging trial with 24-hour sampling; no significant change in GH-deficient adults — Trial-documented but unresolved (see ⚠️ below) (DOI 10.7326/0003-4819-149-9-200811040-00003 vs DOI 10.1210/jcem.81.12.8954023 and DOI 10.1210/jcem.82.10.4297) Trial-documented
  • TSH May deteriorate · 8 weeks — Up at 8 weeks, remaining within normal range — Trial-documented, obese men, n=24 (DOI 10.1046/j.1365-2265.1999.00667.x) Trial-documented
  • Free Testosterone May deteriorate · Over a self-administered cycle — Adversely affected during LGD-4033 + MK-677 co-administration — Case report, attribution unclear — a SARM was co-administered, and these are the biomarkers a SARM is expected to move. Do not attribute to MK-677 (DOI 10.1113/EP090741)
  • Fasting glucose May deteriorate — Not reported in the major trials as primary safety endpoints — No data — a real gap given that fasting glucose and insulin sensitivity both move No data

Safety

  • reliably raises insulin resistance and fasting glucose — the best-characterized effect in this category, not idiosyncratic

Stacking & alternatives

  • Alternative to CJC-1295 — GHRH-receptor agonists rather than ghrelin-receptor agonists — a different upstream input to the same pituitary output. Injectable; no appetite-stimulating mechanism
  • Alternative to Sermorelin — GHRH-receptor agonists rather than ghrelin-receptor agonists — a different upstream input to the same pituitary output. Injectable; no appetite-stimulating mechanism
  • Escalation from CJC-1295 — The documented pattern of movement is toward MK-677 from injectable secretagogues, on the strength of oral convenience and a larger IGF-1 effect. What escalates with it is the metabolic burden — the glucose and insulin-sensitivity signals are MK-677's, not the peptides'
  • Escalation from Ipamorelin — The documented pattern of movement is toward MK-677 from injectable secretagogues, on the strength of oral convenience and a larger IGF-1 effect. What escalates with it is the metabolic burden — the glucose and insulin-sensitivity signals are MK-677's, not the peptides'
  • Escalation from Sermorelin — The documented pattern of movement is toward MK-677 from injectable secretagogues, on the strength of oral convenience and a larger IGF-1 effect. What escalates with it is the metabolic burden — the glucose and insulin-sensitivity signals are MK-677's, not the peptides'
  • Complements BPC-157 — Positioned as recovery-side additions in stack marketing. No study in any species has tested MK-677 with any of them
  • Complements GHK-Cu — Positioned as recovery-side additions in stack marketing. No study in any species has tested MK-677 with any of them
  • Complements TB-500 — Positioned as recovery-side additions in stack marketing. No study in any species has tested MK-677 with any of them

Access & cost

Legally unsettled. Access, where it exists at all, runs through a physician — not a consumer purchase. See the status note above.

No lawful channel to price. As of 2026-08-28 there is no lawful US route to obtain MK-677 for human use, so no legitimate prescription, telehealth, compounding-pharmacy or brand price exists to report. MK-677 is not FDA-approved for any indication; FDA's Pharmacy Compounding Advisory Committee voted 1–13 against making ibutamoren mesylate eligible for compounding under section 503A on 2024-10-29, FDA's own review concluding that "the evaluation criteria weigh against placing ibutamoren mesylate on the list of bulk drug substances that can be used to compound drug products" (PCAC minutes; FDA briefing document). DoD's Operation Supplement Safety states it "is also not legal for use as an ingredient in dietary supplements or any other consumer or commercial products" (OPSS). A substantial gray market nonetheless exists and is documented in the enforcement and analytical record rather than in price reporting: FDA has issued warning letters to multiple companies selling MK-677 products online under "for research use only" labelling, finding that their marketing claims established the products were "intended to be drugs for human use" and therefore unapproved new drugs (FDA, 2025-12-12), and a doping-control research group describes MK-0677 as "one of the most prevalent performance-enhancing compounds currently available online" (DOI 10.1002/dta.3406). Specific price figures for MK-677 were locatable only on seller pages, which Ruling 4 excludes as a source; no journalist-reported figures meeting the brief's standard were found. If Klik needs market-sizing numbers for this compound, they require reporting that does not currently exist in the sources reviewed. ---

Questions

Does MK-677 actually work?
For raising IGF-1, yes, reliably and by a large margin — this is one of the few compounds in the batch where target engagement is beyond dispute, documented in trials of 563 and 65 and 292 and 161 people (DOI 10.1212/01.wnl.0000335163.88054.e7). For producing an outcome anyone would notice, the record is negative: no randomized trial has shown improvement in strength, physical function, cognition, quality of life, or fracture recovery, and the two-year trial in healthy older adults states outright that "increased fat-free mass did not result in changes in strength or function" (DOI 10.7326/0003-4819-149-9-200811040-00003).
Is MK-677 a SARM?
No. It is a ghrelin-receptor agonist with no androgen-receptor activity, classified by anti-doping authorities under growth hormone secretagogues (S2.2.4) rather than with SARMs (S1.2). It is sold by SARM vendors and often taken with SARMs, which is where the confusion comes from. See.
Oral or injectable — which form works?
This is the one question where MK-677 genuinely differs from the rest of this batch, and the answer runs the opposite way from the usual. MK-677 is not a peptide and there is no injectable form in the human literature at all. It is a spiroindoline sulfonamide small molecule that was specifically engineered to survive the gut and be taken by mouth — that was the design objective of the entire Merck programme, and it was demonstrated in dogs at oral doses as low as 0.125 mg/kg before any human dosing (DOI 10.1073/pnas.92.15.7001). That is a canine dose. It is not a human dose and it is not convertible into one — not by bodyweight, not by allometric scaling. No human quantity appears anywhere in this dossier and none can be reconstructed from this figure. Every human trial in, without exception, used oral once-daily administration. So where the injectable peptides in this batch (ipamorelin, CJC-1295, sermorelin, tesamorelin) have no oral evidence, MK-677 has no injectable evidence — and any product marketed as an injectable or nasal MK-677 is outside the entire human literature. Where the marketing outruns the data: the "oral GH" framing is often extended to imply oral growth hormone is available, which it is not. MK-677 is orally active because it is a small molecule that triggers the pituitary; growth hormone itself remains an injectable protein.
Does MK-677 raise blood sugar?
Yes — this is the most consistently replicated adverse finding in the literature. Fasting glucose rose and insulin sensitivity fell in the two-year randomized trial (DOI 10.7326/0003-4819-149-9-200811040-00003); fasting glucose rose from 5.4 to 6.8 mmol/L over four weeks in the first dose-ranging study (DOI 10.1210/jcem.81.12.8954023); a class review names decreased insulin sensitivity as the principal safety concern (DOI 10.1016/j.sxmr.2017.02.004). Note that the 2004 hip-fracture trial excluded people with diabetes at entry, so the trial literature systematically under-samples the people most exposed to this effect.
Why does MK-677 make you so hungry?
Because that is the receptor doing its job. MK-677 is an agonist at GHS-R1a, whose endogenous ligand ghrelin is the body's principal hunger signal (DOI 10.1038/45230). Increased appetite was the most frequently reported side effect in the two-year trial, described there as subsiding after a few months (DOI 10.7326/0003-4819-149-9-200811040-00003). Appetite stimulation is not a side effect that can be engineered away from this mechanism — it is the same mechanism.
Does MK-677 cause water retention?
Trial reports describe "transient, mild lower-extremity edema and muscle pain" as among the most frequent effects in healthy older adults (DOI 10.7326/0003-4819-149-9-200811040-00003), and FDA advisory committee members cited fluid retention among the reasons for voting against compounding eligibility (PCAC minutes). The serious version of this is the congestive heart failure signal that terminated the 2011 hip-fracture trial early — 4 of 62 on drug versus 1 of 61 on placebo (DOI 10.1016/j.archger.2010.10.004; numbers from the FDA briefing document). That signal arose in frail post-surgical elderly patients and has never been evaluated in healthy adults.
Is MK-677 safe?
It has a real, large, long-duration human safety database — which is precisely why the answer is qualified rather than unknown. Across trials it was described as generally well tolerated, with appetite increase, edema, muscle pain, raised fasting glucose and reduced insulin sensitivity as consistent findings, one trial stopped early for congestive heart failure in frail patients, and a published case of transaminitis in an otherwise healthy man in his early 30s after two months of use, resolving after he stopped (DOI 10.1136/bcr-2025-265728). What does not exist is any safety data in healthy young adults, at any duration, and no trial anywhere has run beyond two years.
What happens when you stop taking it?
Nobody has measured it. No trial reported GH, IGF-1, body composition, weight or glucose after discontinuation. Given that roughly 0.8 kg of the fat-free mass gain in the two-year trial was intracellular water and that edema is a recognized effect, some of the gain is plausibly fluid that would not persist — but that is inference, not a documented finding.
Is it detectable in a drug test?
Yes, in urine and in hair. A 2026 controlled-administration study established the minimal detectable dose in hair after a single controlled exposure and after a 90-day regimen, specifically to support interpretation at Court of Arbitration for Sport hearings (DOI 10.1016/j.cca.2025.120578). MK-0677 and its O-dealkylated metabolite are also detectable in equine hair by LC-MS/MS (DOI 10.1002/dta.3406). See. ---

Last reviewed 27 August 2026. Regulatory status verified 27 August 2026.