MK-677 (Ibutamoren) — Evidence Review

What it is

MK-677 (ibutamoren, originally Merck codes MK-0677 / L-163,191) is a non-peptide spiro-indane compound designed at Merck in the mid-1990s as an orally bioavailable growth hormone secretagogue. Unlike injectable GHRH analogues or peptide GH-releasing peptides, it survives digestion and has a roughly 24-hour half-life, allowing once-daily oral dosing. Merck investigated it through the 2000s for age-related loss of muscle/frailty, hip-fracture recovery, and (via an IGF-1/amyloid-clearance hypothesis) Alzheimer's disease. Despite robust "target engagement" (it does raise GH and IGF-1), every major clinical program failed to show meaningful patient benefit, and the hip-fracture trial was stopped early for a heart-failure signal. Merck discontinued development; no New Drug Application was ever filed. It has never been approved for any use in any country and is not a legal dietary-supplement ingredient — it is sold only through unregulated "research chemical" channels.

How it works

MK-677 is a potent, orally active agonist of the growth hormone secretagogue receptor type 1a (GHSR-1a), the same G-protein-coupled receptor activated by endogenous ghrelin, with reported sub-nanomolar affinity. GHSR-1a is expressed mainly in the hypothalamic arcuate nucleus and anterior pituitary. Activation amplifies endogenous pulsatile GH secretion from the pituitary (increasing pulse amplitude while preserving the physiologic pulsatile pattern), which in turn drives hepatic production of insulin-like growth factor-1 (IGF-1). In elderly subjects this restores 24-hour GH output and IGF-1 concentrations toward young-adult ranges. Because it works through the ghrelin receptor, it also stimulates appetite and mildly raises cortisol and prolactin. It has no direct anabolic action on the androgen receptor.

Efficacy — what the human evidence shows

The Institute grades each claimed effect by the strength of the human evidence behind it. Grades are assigned independently for benefit and for harm.

Raises GH secretion and IGF-1 to young-adult range (pharmacodynamic target engagement)Established

Consistently and reproducibly elevates 24-hour GH output and serum IGF-1 across multiple randomized controlled trials. This is a biomarker/surrogate effect, not proof of clinical benefit.

Chapman 1996 JCEM (RCT, n=32 healthy elderly, dose-ranging: 24h mean GH +~97%, IGF-1 restored to young-adult levels); Nass 2008 Ann Intern Med (2-yr RCT, n=65); Sevigny 2008 Neurology (RCT, n=563: IGF-1 +60% at 6 wk, +73% at 12 mo). Replicated human RCT surrogate finding.

Increases fat-free / lean body mass in older adultsProbable

One 2-year RCT showed a modest but statistically significant gain in fat-free mass versus placebo. Body weight also rose, partly from increased appetite and fluid retention.

Nass 2008 Ann Intern Med, double-blind RCT, n=65 healthy adults 60-81 yr, 25 mg/day: fat-free mass change +1.1 kg (MK-677) vs -0.5 kg (placebo), P<0.001; body weight +2.7 vs +0.8 kg, P=0.003. Single main RCT, small n.

Improves muscle strength, physical function, or quality of lifeInsufficient

Trials that measured strength/function did NOT find benefit despite the rise in lean mass and IGF-1 — a key negative finding. The lean-mass gain did not translate into functional improvement.

Nass 2008: no change in muscle strength, function, or quality of life. Adunsky 2011 (hip-fracture RCT): IGF-1 rise not paralleled by improvement in most functional performance measures (e.g. stair-climbing power +12.5 W, 95% CI -10.95 to 35.88, P=0.292).

Slows Alzheimer's disease progressionInsufficient

A large, well-powered 12-month RCT found NO clinical effect on any cognitive or functional endpoint despite clear IGF-1 elevation. This is strong evidence of no benefit, not merely absence of data.

Sevigny 2008 Neurology, double-blind RCT, n=563 mild-to-moderate AD, 25 mg/day, 12 mo: no difference on CIBIC-plus, ADAS-Cog, ADCS-ADL, or CDR-sob. Merck discontinued the program.

Increases bone turnover / improves bonePreliminary

Short-term dosing raises biochemical markers of bone turnover, but longer trials did not establish a meaningful bone mineral density benefit, and regulators flag possible adverse bone effects.

Murphy 1999 J Bone Miner Res: MK-677 increased markers of bone turnover in healthy and functionally impaired elderly adults. No clinical fracture/BMD benefit demonstrated; DoD OPSS lists potential negative effects on bone/BMD.

Safety signals

Harm signals are reported prominently even where the evidence grade is low. Absence of evidence is not evidence of safety.

Congestive heart failure (trial stopped early)Probable

The phase IIb hip-fracture trial was terminated early after more heart-failure events occurred in the drug arm than placebo. The FDA and DoD specifically cite congestive-heart-failure risk as a reason ibutamoren cannot be marketed. This is the single most important harm signal.

Increased fasting glucose / reduced insulin sensitivityProbable

Chronic GH/IGF-1 elevation via ibutamoren raises fasting blood glucose and lowers insulin sensitivity, a consistent, mechanistically expected effect that is a concern for anyone with or at risk of diabetes.

Edema / fluid retentionProbable

Fluid retention and lower-extremity edema are common, an expected consequence of GH-axis stimulation; usually described as mild and transient in trials but part of the same physiology that can worsen heart failure.

Prolactin rise; cortisol largely unchangedPreliminary

Ibutamoren modestly raises prolactin (about 23%, generally within the normal range) through ghrelin-receptor activity. Cortisol is largely unchanged - three controlled trials found no significant change, and only one two-year study showed a small within-group rise of uncertain clinical significance.

Increased appetite, transient muscle pain, mild edemaProbable

Marked appetite stimulation (a ghrelin-mimetic effect), transient muscle pain, and mild fluid retention are the adverse events most consistently reported in trials (Nass 2008: appetite ~67% vs 36% on placebo; muscle pain ~33% vs 9%). Joint pain was not more common than placebo in the pivotal trial, and fatigue was not a reported trial adverse event.

Unknown long-term safety and unregulated product qualityInsufficient

No long-term (multi-year) safety data in the general adult/athletic population, and because the only legal-market products are gray-market 'research chemicals,' actual identity, dose, and purity are unverified. Absence of evidence is not evidence of safety.

Human trials on record

Study / registry	Phase	Population	Key result
Chapman et al. 1996, J Clin Endocrinol Metab 81(12):4249-4257	Early-phase RCT (dose-ranging)	32 healthy elderly adults (64-81 yr), 2/10/25 mg once daily for 14-28 days	24-hour mean GH increased ~97%; IGF-1 restored to young-adult concentrations within weeks. Established oral GH/IGF-1 axis stimulation.
Murphy et al. 1999, J Bone Miner Res 14(7):1182-1191	Phase II RCT	Healthy and functionally impaired elderly adults	Oral MK-677 increased biochemical markers of bone turnover; no demonstrated clinical bone benefit.
Nass et al. 2008, Ann Intern Med 149(9):601-611 (PMID 18981485)	Phase II RCT (2-year, double-blind, modified crossover)	65 healthy adults 60-81 yr, 25 mg/day	Fat-free mass +1.1 kg vs -0.5 kg placebo (P<0.001); GH/IGF-1 to young-adult range; BUT no gain in strength, function, or quality of life. Fasting glucose rose and insulin sensitivity fell; transient edema; cortisol rose.
Sevigny et al. 2008, Neurology 71(21):1702-1708 (PMID 19015485)	Phase II/III RCT (12-month)	563 patients with mild-to-moderate Alzheimer's disease, 25 mg/day	IGF-1 rose ~60% (6 wk) to ~73% (12 mo) confirming target engagement, but NO effect on any cognitive/functional endpoint (CIBIC-plus, ADAS-Cog, ADCS-ADL, CDR-sob). Program discontinued.
Adunsky et al. 2011, Arch Gerontol Geriatr 53(2):183-189	Phase IIb RCT (terminated early)	123 elderly hip-fracture patients (62 MK-0677 / 61 placebo), 25 mg/day for 24 weeks	IGF-1 rose (~+51 ng/mL) but functional performance did not improve. Trial stopped early for a congestive-heart-failure safety signal (4/62 [6.5%] on drug vs 1/61 [1.7%] on placebo); concluded unfavorable safety profile in this population.

Legal & regulatory status

United States

Not FDA-approved for any indication; investigational new drug only, development discontinued by Merck. The FDA treats ibutamoren as an unapproved drug that cannot lawfully be sold as a dietary supplement (it was studied as a drug before any supplement marketing), and has issued warning letters to companies selling it. It is on the U.S. Department of Defense Prohibited Dietary Supplement Ingredients List. Sold only via unregulated gray-market 'research chemical' channels with no assurance of identity, purity, or dose.

Anti-doping (WADA)

Prohibited at all times (in- and out-of-competition) under Section S2 of the WADA Prohibited List — Peptide Hormones, Growth Factors, Related Substances and Mimetics. Ibutamoren is explicitly named among prohibited growth hormone secretagogues (alongside anamorelin, capromorelin, ipamorelin, lenomorelin/ghrelin, macimorelin, tabimorelin). Multiple athletes have been sanctioned for ibutamoren.

Other jurisdictions

Prohibited by the DoD for service members (OPSS). Not an approved medicine in the EU, UK, Australia, or Canada.

The bottom line

MK-677 is not a SARM — it is an oral ghrelin-receptor (GHSR-1a) agonist / growth hormone secretagogue. The one thing it does reliably is raise GH and IGF-1 to young-adult levels, and one 2-year trial showed a small gain in lean body mass. But that is where the good news ends: across large, well-run trials it failed to improve muscle strength, physical function, quality of life, or Alzheimer's progression, and its hip-fracture trial was stopped early over a congestive-heart-failure signal. It consistently raises fasting glucose, lowers insulin sensitivity, and causes fluid retention/edema. It has never been approved anywhere, cannot legally be sold as a supplement, is banned by WADA and the U.S. military, and is available only as an unverified gray-market research chemical. Net: robust biomarker changes, unproven clinical benefit, and real cardiovascular and metabolic safety concerns.

References

Design and biological activities of L-163,191 (MK-0677): a potent, orally active growth hormone secretagoguePatchett et al., Proc Natl Acad Sci USA, 1995;92(15):7001-7005
Stimulation of the growth hormone (GH)-insulin-like growth factor I axis by daily oral administration of a GH secretagogue (MK-677) in healthy elderly subjectsChapman et al., J Clin Endocrinol Metab, 1996;81(12):4249-4257
Oral administration of the growth hormone secretagogue MK-677 increases markers of bone turnover in healthy and functionally impaired elderly adultsMurphy et al., J Bone Miner Res, 1999;14(7):1182-1191
Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trialNass et al., Ann Intern Med, 2008;149(9):601-611 (PMID 18981485)
Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trialSevigny et al., Neurology, 2008;71(21):1702-1708 (PMID 19015485)
MK-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip fracture: a multicenter, randomized, placebo-controlled phase IIb studyAdunsky et al., Arch Gerontol Geriatr, 2011;53(2):183-189
Performance Enhancing Substance: MK-677 (Ibutamoren) — FDA/DoD status, congestive heart failure and metabolic risksU.S. Department of Defense, Operation Supplement Safety (OPSS), 2024/2026
The Prohibited List — S2 Peptide Hormones, Growth Factors, Related Substances and Mimetics (growth hormone secretagogues incl. ibutamoren)World Anti-Doping Agency (WADA)

SARMS Institute Research Desk. Compiled from primary sources. Last updated 20 July 2026.
This review is for education and does not provide medical or legal advice. No SARM is approved for human use.