MK-677 (Ibutamoren) is an orally active, non-peptide growth hormone secretagogue investigated for its ability to stimulate growth hormone and IGF-1 secretion. As of 2026 it remains an investigational compound, not FDA-approved for any indication in the United States, prohibited in sport by WADA, and placed by FDA in Category 2 for both 503A and 503B compounding over a congestive heart failure signal.
Key takeaways
MK-677 acts at the GHSR1a receptor, increasing pulsatile GH and sustained IGF-1 in clinical studies.
It is orally bioavailable, distinguishing it from injectable GH secretagogues.
No FDA-approved indication exists as of 2026; trials have explored sarcopenia, hip fracture recovery, and GH deficiency.
FDA has placed ibutamoren in Category 2 for both 503A and 503B compounding, citing the potential for congestive heart failure in certain patients. A Phase IIb hip fracture trial was terminated early over that signal.
Reported adverse effects include increased appetite, fluid retention, elevated fasting glucose, and reduced insulin sensitivity.
WADA prohibits ibutamoren by name at S2.2.4, at all times, as a non-Specified Substance.
What is MK-677?
MK-677 is the development code for an orally bioavailable, non-peptidic growth hormone secretagogue developed in the 1990s by Merck Research Laboratories, designed to trigger endogenous GH release through the GHSR1a receptor. It is the same molecule referred to by its INN, Ibutamoren (sometimes Ibutamoren mesylate or MK-0677). The NIH substance registry records “ibutamoren [INN]” under INN identifier 7682. The original medicinal chemistry is published in Patchett et al., 1995 (free full text at PMC41459).
The landmark pharmacology trial by Chapman et al. (1996, Journal of Clinical Endocrinology & Metabolism) studied 32 healthy adults aged 64 to 81 across four arms: placebo, 2 mg, 10 mg, and 25 mg daily.
At the 25 mg/day dose, after two weeks, mean 24-hour GH concentration rose 97 ± 23% versus baseline (P < 0.05). That is the integrated 24-hour profile, not a peak or a stimulated response, and it is the highest of the four arms.
IGF-I over the same window, reported as absolute concentrations: 141 ± 21 µg/L at baseline, 219 ± 21 at two weeks, 265 ± 29 at four weeks (P < 0.05).
And in the same subjects, fasting glucose rose from 5.4 ± 0.3 to 6.8 ± 0.4 mmol/L at four weeks (P < 0.01).
The paper’s own conclusion is narrower than the summaries of it: at 25 mg/day, MK-677 restored serum IGF-I concentrations to those of young adults. IGF-I only, top dose only.
Quick reference for clinicians:
Origin: Merck Research Laboratories; compound class = growth hormone secretagogue (GHS).
Route: oral, which distinguishes MK-677 from injectable peptides such as GHRP-6 and ipamorelin.
Duration of action: orally active with pharmacokinetics suitable for once-daily administration, and the hormonal effect outlasts plasma exposure (Smith and Thorner, 2023). Controlled human trials used 25 mg once daily and IGF-1 stays elevated across the full 24-hour interval, so plasma half-life is a poor guide to dosing frequency. No human terminal half-life has been published in the peer-reviewed literature. Figures circulating online (commonly “4–6 hours”) trace back to a canine study and are not human data.
Current status: investigational. Not approved for any therapeutic indication in the United States as of 2026.
Nomenclature: “MK-677,” “MK-0677,” and “Ibutamoren” all refer to the same molecule.
What is Ibutamoren and how does it differ from other GH secretagogues?
Ibutamoren is the international nonproprietary name (INN) for MK-677. It differs from peptide secretagogues primarily by being orally active, longer-acting, and structurally non-peptidic, which is why it has been studied as a chronic oral therapy rather than a subcutaneous injection.
A note on terminology, because it is a useful tell for source quality. Chapman 1996 calls MK-677 “a GH-releasing peptide mimetic” — a mimetic of the synthetic GHRP-6 class. It does not call it a ghrelin mimetic, and it could not have: ghrelin was not identified until Kojima et al., Nature 1999;402(6762):656–60. The 1997 companion paper from the same group uses the same pre-ghrelin language. The “oral ghrelin mimetic” framing belongs to Nass et al. 2008, where it appears in the title. Any source attributing ghrelin language to a 1996 paper has back-dated it.
The longest randomized trial of MK-677 in healthy older adults is Nass et al. (2008, Annals of Internal Medicine): a 2-year, double-blind, randomized, placebo-controlled, modified-crossover trial at 25 mg once daily, with 71 randomized and 65 completing year 1. Twelve months was the pre-specified primary endpoint window, not the trial length.
At 12 months, fat-free mass fell 0.5 kg in the placebo group and rose 1.1 kg in the MK-677 group (95% CI 0.7 to 1.5 kg; P < 0.001), an increase of 1.6 kg relative to placebo.
The authors’ conclusion, verbatim: “Over 12 months, the ghrelin mimetic MK-677 enhanced pulsatile growth hormone secretion, significantly increased fat-free mass, and was generally well tolerated. Long-term functional and, ultimately, pharmacoeconomic, studies in elderly persons are indicated.”
What the same trial found alongside that gain, and what belongs in any clinical read of it:
“Increased fat-free mass did not result in changes in strength or function.” No significant differences in abdominal visceral fat or total fat mass.
Fasting blood glucose rose an average of 0.3 mmol/L (5 mg/dL; P = 0.015) and insulin sensitivity decreased. HbA1c rose 0.2% (P = 0.002). Sixteen MK-677 subjects crossed from below 5.6 into the 5.6–6.1 mmol/L fasting glucose band; eight finished year 1 above 6% HbA1c; four were blindly back-titrated to 10 mg, two of them for rising glucose.
The gain is “fat-free mass,” the paper’s own endpoint term, and the authors attribute it to intracellular water rather than contractile tissue. Appendicular lean gain was 0.5 kg, thigh muscle cross-sectional area did not increase at all, and limb fat rose more on drug than placebo (1.1 kg vs 0.24 kg; P = 0.001).
IGF-I rose 1.5-fold, but was sustained within the young-adult normal range in only 22 of 43 subjects, and returned to pretreatment levels one month after crossover.
Generalizability, for the record: healthy adults aged 60 to 81, enrolled 1998 to 2003, excluding BMI ≥ 35, strenuous exercise over 60 minutes per day, smoking, diabetes, malignancy history, untreated hypertension, and thyroid disease. The trial says nothing about younger patients, metabolic disease, or performance use.
Mechanism contrast with other GH secretagogues:
| Class | Examples | Route |
|---|---|---|
| Peptide GHRPs (ghrelin mimetics) | ipamorelin, GHRP-2, GHRP-6 | Injectable |
| GHRH analogs | sermorelin, CJC-1295, tesamorelin | Injectable |
| Non-peptide GHS | MK-677 / Ibutamoren | Oral |
The congestive heart failure signal
This is the part of the record that outranks the efficacy data.
A multicenter, randomized, placebo-controlled Phase IIb study in patients recovering from hip fracture (Adunsky et al., Archives of Gerontology and Geriatrics, 2011;53(2):183–9) was terminated early after “a safety signal of congestive heart failure in a limited number of patients.” The authors concluded that MK-677 “has an unfavorable safety profile in this patient population.”
The trial’s IGF-1 response was robust (P < 0.001) and gait speed reached significance (P = 0.011), but that rise “was not paralleled by improvement in most functional performance measures.” The registered eligibility criteria did not list heart failure among the exclusions, though they do exclude “an unstable medical condition.”
FDA has since stated the same concern in its own voice. In a December 19, 2025 warning letter, FDA wrote that ibutamoren “is an active ingredient not approved by FDA, and therefore its safety and efficacy have not been established,” that its use “may increase the potential for congestive heart failure in certain individuals,” and that “FDA has determined that ibutamoren is excluded from the definition of a dietary supplement under section 201(ff)(3)(B)(ii).”
This signal carries no effect size, event counts, or comparator in the primary literature. Treat it as what it is: a safety signal that terminated a trial early, not a quantified risk.
Note that MK-677 development did not stop over it. A related compound, LUM-201, is in an actively recruiting Phase 3 trial (NCT06948214).
Regulatory and legal status (2026)
FDA compounding status. Ibutamoren mesylate is in Category 2 — bulk drug substances that may present significant safety risks — for both pathways: 503B (December 29, 2022) and 503A (September 29, 2023), citing the potential for congestive heart failure in certain patients. FDA’s Pharmacy Compounding Advisory Committee voted 13 to 1 against adding it to the 503A Bulks List on October 29, 2024.
FDA approval status. No approved indication in the United States. Per FDA’s own December 2025 warning letter, ibutamoren “is an active ingredient not approved by FDA, and therefore its safety and efficacy have not been established.”
A database result that looks like a contradiction, and isn’t. FDA’s NDC Directory returns three active ibutamoren mesylate registrations as of August 7, 2026, one of them categorized “BULK INGREDIENT FOR HUMAN PRESCRIPTION COMPOUNDING,” all marked as unfinished bulk API. That listing is a registration formality. It is not an approval, and it does not change anything above.
Historical compounding volume. FDA describes the extent of historical compounding with ibutamoren as unclear, and notes that no outsourcing facility has reported compounding it since 2020.
WADA. The 2026 Prohibited List (effective January 1, 2026) names it directly at S2.2.4 as “ibutamoren (MK-677),” among growth hormone secretagogues and their mimetics. All S2 substances are non-Specified Substances, prohibited at all times, in and out of competition.
Consumer market. MK-677 is widely sold online as a “research chemical.” These products are not pharmaceutical grade, are not subject to USP standards, and their legal status varies by jurisdiction. FDA has issued warning letters to sellers marketing it as a dietary supplement. Clinicians should counsel patients accordingly and avoid endorsing non-regulated sourcing.
About VITL
VITL is a unified ePrescribing platform for clinics that work with licensed 503A compounding pharmacies and FDA-registered 503B outsourcing facilities. Clinics typically juggle five to seven pharmacy portals to place orders, compare prices, and track fulfillment. VITL consolidates those relationships into a single dashboard: one login, transparent price comparison, batch ordering, and order tracking across partner pharmacies.
The point isn’t more features. It’s removing the admin work that pulls clinicians away from patient care. Beautifully simple ePrescribing.
Nothing on this page should be read as suggesting MK-677 is an approved, available, or appropriate compounded therapy. It is an investigational compound that FDA has placed in Category 2 for both compounding pathways.
References and further reading
Reviewed by VITL’s clinical content team in consultation with licensed prescribers; references drawn from peer-reviewed endocrinology literature and federal regulatory documents. Last updated 2026.
Chapman IM, Bach MA, Van Cauter E, et al. “Stimulation of the growth hormone (GH)-insulin-like growth factor I axis by daily oral administration of a GH secretogogue (MK-677) in healthy elderly subjects.” J Clin Endocrinol Metab. 1996 Dec;81(12):4249–57. PMID 8954023. DOI 10.1210/jcem.81.12.8954023.
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 Nov 4;149(9):601–11. PMID 18981485. DOI 10.7326/0003-4819-149-9-200811040-00003.
Adunsky A, Chandler J, Heyden N, et al. “MK-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip fracture: a multicenter, randomized, placebo-controlled phase IIb study.” Arch Gerontol Geriatr. 2011 Sep–Oct;53(2):183–9. PMID 21067829.
Smith RG, Thorner MO. J Gerontol A Biol Sci Med Sci. 2023;78(Suppl 1):38–43. PMID 37325967.
Kojima M, et al. “Ghrelin is a growth-hormone-releasing acylated peptide from stomach.” Nature. 1999;402(6762):656–60. PMID 10604470.
Patchett AA, et al. Proc Natl Acad Sci U S A. 1995. PMC41459.
FDA, Bulk Drug Substances Nominated for Use in Compounding Under Sections 503A and 503B — Category 2 listings for ibutamoren mesylate.
FDA warning letter 718252 (CDER), December 19, 2025.
World Anti-Doping Agency, 2026 Prohibited List, S2.2.4.
This article is for clinician education only. It is not medical advice and does not endorse the use, prescription, or sourcing of any investigational compound.
