MK-677 (Ibutamoren) (Ibutamoren mesylate) — what it does, evidence, and safety

What it is

MK-677 (Ibutamoren) is a growth hormone releaser that prompts the pituitary gland to release the body's own growth hormone by acting on the ghrelin (hunger hormone) receptor. Unlike most compounds here, it's taken orally, as a pill or liquid, and it isn't actually a peptide, it's a small-molecule drug. It's pursued for muscle, sleep, and anti-aging effects, but a two-year trial found only modest, mostly-water gains, and a hip-fracture trial in older adults was stopped early after more heart-failure cases in the MK-677 group. It's not FDA-approved for any use, it's banned in drug-tested sport, and it's now in Phase 3 trials for childhood growth hormone deficiency.

What the research found

MK-677 (ibutamoren) is an oral compound studied to raise growth hormone and IGF-1. Early pharmacology showed daily oral MK-677 raised those hormones in healthy older adults. But a two-year randomized trial reported only a small increase in fat-free mass — largely water rather than muscle — with no strength improvement and worsened insulin sensitivity, and a Phase 2b trial in elderly hip-fracture patients was stopped early after more congestive heart failure in the MK-677 group than placebo. The body-composition and sleep uses people pursue are not confirmed by trials proving those outcomes.

Status and regulatory position

Not FDA-approved for any indication. Originally developed by Merck through phase 2 / phase 2b clinical trials in the late 1990s and 2000s for adult growth hormone deficiency, age-related frailty, hip fracture recovery, and Alzheimer's disease — none of which advanced to FDA approval. A multicenter phase 2b hip fracture trial (Adunsky 2011) was terminated early by the Data Safety Monitoring Board after identifying a higher congestive heart failure rate in the MK-677 group than placebo[³] — a safety signal that has materially shaped the regulatory and clinical context for MK-677. Currently under phase 3 development by Lumos Pharma (the OraGrowtH trial program in pediatric GHD) — if successful, would represent the first oral GH secretagogue to achieve FDA approval. Not DEA-scheduled. WADA-banned in regulated sport — explicitly listed as *"ibutamoren (MK-677)"* under Section S2.2.4 (Growth Hormone Releasing Factors → growth hormone secretagogues / GHS) of the 2026 Prohibited List, the same subsection as Ipamorelin. Currently sold as a research compound (not a peptide; technically a small-molecule drug) outside the FDA-approved framework.

Safety

MK-677 is taken orally and is not a peptide. It is not FDA-approved, and a clinical trial was stopped early over a heart-failure safety signal; it also worsened insulin sensitivity in trials. It is banned in regulated sport (WADA Prohibited List, Section S2.2.4). VialWise is a research and educational reference, not medical advice — consult a licensed professional.

Disclosures

⚠️ For research and educational purposes only. MK-677 is not FDA-approved for any indication and is currently under phase 3 development by Lumos Pharma for pediatric GHD. Information in this entry is informational, not medical advice. Always confirm dose calculations with the in-app calculator and consult appropriate professional guidance before any protocol decisions.

⚠️ MK-677 is not a peptide. It is a small-molecule, non-peptide, spiropiperidine drug. This entry exists in the Vialwise library because researchers running peptide protocols frequently use MK-677 alongside peptide stacks (CJC-1295, Ipamorelin, etc.) — and because MK-677 acts on the same ghrelin receptor (GHS-R1a) as the peptide GHRP class (Ipamorelin, GHRP-2, GHRP-6). MK-677 is structurally a non-peptide oral drug; mechanistically a ghrelin receptor agonist. This is a different compound class from the peptides that dominate the rest of the Vialwise library. Researchers should be explicit with themselves about which compound class they are using.

⚠️ Important safety signal: elevated congestive heart failure rate observed in the Adunsky 2011 phase 2b hip fracture trial. A multicenter, randomized, placebo-controlled phase 2b trial in 123 elderly hip fracture patients (Adunsky et al., 2011) was terminated early by the Data Safety Monitoring Board after identifying an elevated congestive heart failure rate in the MK-677 group versus placebo.[³] This safety signal was a major factor preventing the drug from advancing to phase 3 in the elderly-frailty population at that time. The CHF risk appears concentrated in elderly patients with underlying cardiac vulnerability — but the safety signal is meaningful for any researcher considering MK-677, particularly those with cardiovascular risk factors. The Lumos Pharma OraGrowtH phase 3 program in pediatric GHD addresses a different population (treatment-naive prepubertal children) where the cardiovascular risk profile is fundamentally different.

⚠️ Oral bioavailability — distinct from the peptide GHRPs. MK-677's non-peptide spiropiperidine structure confers resistance to proteolysis and enables efficient oral absorption. Peak plasma concentrations within ~1 hour of oral dose; terminal half-life ~24 hours, supporting once-daily oral dosing. This is a fundamental architectural difference from the injectable peptide GHRPs (Ipamorelin, GHRP-2, GHRP-6) covered elsewhere in this library — same receptor target, completely different molecule class and administration route. Researchers should not confuse MK-677 with the peptide GHRPs even though they share the GHS-R1a target.

Quick reference

Compound class	Non-peptide spiropiperidine drug; ghrelin receptor (GHS-R1a) agonist. Not a peptide. Same target as the peptide GHRPs (Ipamorelin, GHRP-2) but different molecule class.
Common product format	Oral capsule or tablet or per dose. Compounded oral liquid formulations also exist in research-community supply. Not injectable.
Frequency	Once daily (oral).
Half-life	Plasma terminal half-life: ~24 hours — exceptionally long for a GHS-R1a agonist; supports once-daily dosing. Peak plasma concentration within ~1 hour of oral dose.
Route	Oral (this is the defining feature relative to the peptide GHRPs).
Onset of action	Acute GH/IGF-1 elevation detectable within hours of first dose. Subjective effects (appetite increase — the most consistent — plus sleep changes and body composition) typically reported within 1–2 weeks of consistent bedtime dosing.

In depth

MK-677 (ibutamoren mesylate; developmental codes MK-0677 / L-163,191) is a non-peptide spiropiperidine drug developed by Merck in the 1990s as an orally bioavailable growth hormone secretagogue. The molecule binds and activates the ghrelin receptor (GHS-R1a) at pituitary somatotrophs, mimicking the GH-stimulating effect of endogenous ghrelin. MK-677 is the only non-peptide ghrelin-receptor agonist that has reached extensive clinical development — its non-peptide spiropiperidine structure confers resistance to proteolysis and enables efficient gastrointestinal absorption, both of which are exceedingly rare among GHS-R1a agonists. Its long half-life (~24 hours) supports once-daily dosing, distinguishing it from the short-half-life injectable peptide GHRPs (Ipamorelin ~2 hours, GHRP-2 ~30 minutes).

Mechanism vs the peptide GHRPs. MK-677 and the peptide GHRPs (Ipamorelin, GHRP-2, GHRP-6, hexarelin) all bind the same ghrelin receptor (GHS-R1a) at pituitary somatotrophs and trigger the same GH-release pathway. The practical differences are pharmacokinetic and route: MK-677 is oral and long-acting (~24h half-life); Ipamorelin and the peptide GHRPs are injectable and short-acting (~2 hours or less). Mechanistically, the GH-release effect is similar — but MK-677's sustained 24-hour exposure produces a continuous baseline GH/IGF-1 elevation rather than the pulsatile pattern that injectable peptide GHRPs preserve. This pharmacokinetic difference has practical consequences: - MK-677 sustains elevated IGF-1 around the clock — useful for body-composition / anabolic effects, but more likely to produce IGF-1-mediated side effects (insulin resistance, fluid retention, theoretical malignancy concerns) than pulsatile GHRP regimens. - Pulsatile GHRP regimens preserve more physiologic GH dynamics but require multiple-times-daily injection (vs MK-677's once-daily oral dosing). - Researchers selecting between MK-677 and Ipamorelin are essentially choosing between sustained-exposure-via-oral-route (MK-677) vs pulsatile-via-injection (Ipamorelin). See [ipamorelin.md](./ipamorelin.md).

Clinical development history. Merck advanced MK-677 through phase 2 / phase 2b development in multiple indications during the late 1990s and 2000s: - Adult growth hormone deficiency — pharmacology established (Murphy 1998 demonstrated GH/IGF-1 axis activation in healthy elderly subjects)[¹] - Age-related frailty / sarcopenia — Nass 2008 (Annals of Internal Medicine, n=65 healthy older adults, 2-year modified-crossover RCT with primary endpoints at 1 year MK-677 vs placebo) reported FFM increase of +1.1 kg vs placebo, but no improvement in muscle strength and worsening of insulin sensitivity[²] - Hip fracture recovery — Adunsky 2011 phase 2b trial (n=123 elderly hip fracture patients) terminated early by DSMB after identifying an elevated congestive heart failure rate in the MK-677 group versus placebo[³] - Alzheimer's disease — Sevigny 2008 randomized trial in mild-to-moderate Alzheimer's reported no clinical effect on AD progression - None of these programs advanced to FDA approval. Merck wound down the elderly-population MK-677 program after the Adunsky 2011 safety signal.

Lumos Pharma OraGrowtH program (currently active phase 3). Lumos Pharma acquired the MK-677 program and is currently conducting a multicenter, randomized, double-blind, placebo-controlled phase 3 trial (ClinicalTrials.gov NCT06948214; recruiting, started 2026-05-20; n=150; randomized 2:1 LUM-201:placebo) in treatment-naive prepubertal children with growth hormone deficiency[⁵][⁶]. If successful, this would represent the first oral GH secretagogue to achieve FDA approval. The pediatric GHD population is regulatorily distinct from the adult elderly-frailty population — children with GHD have a different cardiovascular risk profile, and the OraGrowtH program is the path being pursued to bring MK-677 to FDA approval. A 2025 review of new directions in pediatric growth hormone treatment (Stawerska) discusses preliminary data on oral ibutamoren in children with partial GHD, consistent with this program's rationale.[⁹]

Regulatory status (US). MK-677 is not FDA-approved for any indication as of this entry's last-updated date. The Lumos Pharma phase 3 program is currently active. MK-677 is classified as an Investigational New Drug in the United States, meaning it is not legally available for general human use outside the FDA-approved clinical trial framework. Not DEA-scheduled. Research-community supply chains exist (oral capsules and powder formulations dispensed for "research use only" through compounding pharmacies and overseas suppliers) but operate outside the FDA-approved framework.

Regulatory status (sport — WADA). MK-677 is explicitly listed under Section S2.2.4 (Growth Hormone Releasing Factors → growth hormone secretagogues / GHS) of the 2026 WADA Prohibited List, in the same subsection as Ipamorelin and other GHS-class compounds. Verbatim from the canonical PDF: *"growth hormone secretagogues (GHS) and their mimetics [e.g. anamorelin, capromorelin, ibutamoren (MK-677), ipamorelin, lenomorelin (ghrelin), macimorelin and tabimorelin]"*[⁴] — MK-677 is named explicitly. Prohibited at all times in regulated sport.

Common research interests. Despite the absence of FDA approval and the Adunsky 2011 safety signal, MK-677 is widely used in research-community contexts for: - Body composition / anabolic effects — driven by sustained GH/IGF-1 elevation; the most common research-community use case - Sleep quality — MK-677 has been reported to increase REM sleep duration (20% in young subjects, 50% in older subjects in a small early study); sleep-quality improvement is one of the consistently reported subjective effects - Adjunct to peptide stacks — sometimes combined with Ipamorelin (despite same-receptor redundancy at the GHS-R1a target — see Stacks section), CJC-1295, or testosterone - Anti-aging / longevity contexts — driven by the original Merck adult-frailty-and-elderly-population development rationale

The Adunsky 2011 CHF safety signal is meaningful clinically but has not deterred research-community use; researchers using MK-677 should be explicit with themselves about cardiovascular risk profile, particularly with prolonged use or pre-existing cardiac risk factors.

Reported side effects

Commonly reported

Increased appetite (ghrelin-receptor-mediated) — the most consistently reported side effect. Dose-dependent: manageable for most users; can be intense ("hunger" within 1–2 hours of dosing). Most users report appetite normalization after 2–4 weeks as ghrelin receptor sensitivity adjusts; in others appetite stimulation persists.
Water retention / mild edema — particularly in the first 1–2 weeks of dosing; typically resolves with continued use or mild dose reduction
Insulin resistance / impaired glucose tolerance — well-documented in the Nass 2008 trial; HbA1c and fasting glucose elevation observable within 6–12 months of continuous use
Mild fatigue or lethargy — particularly during initial dose escalation
Sleep architecture changes — typically increased REM sleep duration; occasionally reported as more vivid dreams
Mild myalgia or arthralgia — uncommon; consistent with the broader GH-axis side-effect profile

Serious

New or worsening symptoms of congestive heart failure (peripheral edema with shortness of breath, exercise intolerance, paroxysmal nocturnal dyspnea) — given the Adunsky 2011 safety signal, MK-677 should be discontinued at the first sign of CHF symptoms, particularly in older patients or those with pre-existing cardiac risk
New or worsening glucose intolerance / hyperglycemia
Severe edema or symptoms suggestive of fluid overload
New cardiovascular symptoms (chest pain, dyspnea, palpitations) — possible LV strain or arrhythmia
Signs of liver stress (unusual fatigue, right-upper-quadrant pain, dark urine, jaundice) — a 2025 case report (Cobani et al.) described transaminitis in a healthy man after ~2 months of MK-677 that normalized after discontinuation; single-case evidence, but a reason to monitor liver enzymes on-cycle[⁷]
Sudden severe abdominal pain — a single 2026 case report (Jaffry et al.) described spontaneous splenic rupture in a man using MK-677 together with the sarm rad-140; the authors frame the compounds' role as speculative and the case is confounded by co-use, so this is a low-evidence signal only[⁸]
Severe psychiatric changes (uncommon but reported with very high doses)

Contraindications and warnings

Pre-existing congestive heart failure or significant cardiac vulnerability — strong caution per the Adunsky 2011 phase 2b CHF safety signal

Active malignancy — IGF-1 elevation may promote cancer progression

Diabetes / impaired glucose tolerance — caution; MK-677 worsens insulin sensitivity

Pregnancy and lactation — no data; default to contraindicated

Pediatric use (outside the Lumos Pharma OraGrowtH trial framework) — the active phase 3 program operates under specialist supervision in a controlled trial population; off-label pediatric use outside this framework is strongly contraindicated

Concurrent corticosteroid use — caution; corticosteroids may interfere with MK-677's GH-stimulating effect

Pregnancy and lactation: contraindicated (no human data).

Long-term safety in healthy adults is essentially unknown — no multi-year human safety dataset exists for the research-community continuous-use pattern.

Regulatory note (US): MK-677 is not FDA-approved; classified as an Investigational New Drug. Distribution outside the FDA-approved clinical trial framework is regulated under the broader compounding-pharmacy and "research use only" framework that applies to most non-FDA-approved compounds.

Regulatory note (sport): MK-677 / ibutamoren is explicitly listed in WADA 2026 Prohibited List Section S2.2.4 alongside Ipamorelin and other GHS-class compounds; prohibited at all times in regulated sport.[⁴]

Key terms

Growth hormone secretagogue: A compound that signals the body to release its own growth hormone, rather than supplying growth hormone directly.
Ghrelin receptor: a receptor that, when activated, triggers growth hormone release and hunger.
Oral bioavailability: how well a drug is absorbed when taken by mouth rather than injected.
IGF-1: a growth factor the liver makes in response to growth hormone; used as a lab marker (and, for igf-1 lr3, a growth factor that drives tissue and muscle growth).
WADA Prohibited List: The list of substances banned in regulated sport by the World Anti-Doping Agency.

Sources

Related entries

CJC-1295 — discussed together in this entry's stacks section
Testosterone — discussed together in this entry's stacks section
CJC-1295 / Ipamorelin Blend — same mechanism class
GHRP-2 — same mechanism class
GHRP-6 — same mechanism class
Hexarelin — same mechanism class